Pharmacokinetics/ADME IV: Drug Excretion: Overview of Drug Metabolism
Most drugs and drug molecules are excreted by the: a) liver b) kidneys c) gall bladder d) lungs
*The answer B.* Excretion of drugs occurs primarily through the kidneys, although small quantities of drug may be detected in the faeces. Drugs that are detected in the faeces are eliminated from the body through the bile. Drugs may also be detected in sweat, saliva, hair, tears, and exhaled air, although these are not considered routes of excretion since the quantities usually detectable are very low.
Which of the following acids has the highest degree of ionization in an aqueous solution? (a) Aspirin pKa = 3.5 (b) Indomethacin pKa = 4.5 (c) Warfarin pKa = 5.1 (d) Ibuprofen pKa = 5.2 (e) Phenobarbital pKa = 7.4
*The answer is A.* Aspirin has the highest degree of ionization in an aqueous solution. Therefore, it will be excreted faster.
The elimination of a drug and its numerous metabolites is described as being heavily dependent on Phase II metabolic reactions? Which of the following is a Phase II reaction? A. Glucuronidation B. Decarboxylation C. Ester hydrolysis D. Nitro reduction E. Sulfoxide formation
*The answer is A.* Biotransformation reactions involving the oxidation, reduction, or hydrolysis of a drug are classified as Phase I (or nonsynthetic) reactions; these reactions may result in either the activation or inactivation of a pharmacologic agent. There are many types of these reactions; oxidations are the most numoerous. Phase II (ocassionally caled synthetic) reactions, which elmost always result in the formation of an inative product, invovle conjugation of the drug (or its derivative) with an amino acid, carbohydrate, acetate, sulfate,- or glucoronic acid as noted in the question. The conjugated form(s) of the drug or its derivates may be more easily excreted than the parent compound.
A 28-year-old man with seborrheic dermatitis is prescribed a topical corticosteroid crème by his derma-tologist in hopes of alleviating the chronic rash and erythema on the cheeks. Which of the following steps is most critical to achieve a therapeutic drug concentration in plasma? (A) Absorption (B) Distribution (C) Elimination (D) Glycosylation (E) Metabolism
*The answer is A.* Drug absorption from the site of administration, in this case via the topical route, allows the medication to enter into the skin and then into the plasma. Following this step, the medication can distribute into tissues and also be metabolized in tissues. (B) Distribution occurs following absorption of the drug from the site of administration. (C) Elimination involves removal of the drug from the body via urine, bile, or feces. (D) Glycosylation is not a step in the process of drug pharmacokinetics. (E) Metabolism of drugs occurs in the kidneys or liver after the drug has achieved adequate levels in tissues.
Drug biotransformation is classically: a) Divided into: Phase I - Functionalization; Phase II - Conjugation. b) Divided into: Phase I - drug degradation ; Phase II - recycling of the metabolites for the synthesis of new amino acids. c) Performed mainly in the muscles since muscles account for the largest mass of tissue in our body. d) Happens spontaneously after the expiration date of the drug. e) Refers to drug degradation mediated by the bacteria that live in the digestive track.
*The answer is A.* Drug biotransformation is classically divided into two phases - Phase I and Phase II. Phase I reactions are biotransformation reactions and phase II reactions are conjugation reactions.
The P-glycoprotein is a multidrug transmembrane transporter protein that transports medications across cell membranes. Functions of this protein include (A) Pumping drugs into the urine for excretion (B) Transport of drugs into liver hepatocytes (C) Transport of drugs into fetal circulation for fetal treatment (D) Transport of drugs from the intestinal lumen to the circulation (E) Transport of drugs from the bloodstream into brain cells
*The answer is A.* The P-glycoprotein is a multidrug transmembrane trans-port protein that transports medication across cell membranes. In the kidney, responsibilities include pumping drugs into the urine for excretion (B) This protein excretes drugs into bile for excretion in feces. (C) This protein transports drugs out of fetal circulation via the placenta into the maternal circulation. (D) This protein transports drugs from the circulation into the intestinal lumen. (E) This protein transports blood out of the brain cells to protect them from drug toxicities.
A 38-year-old woman presents to her psychiatrist with a request to try a different antidepressant medication, since she doesn't feel her current medication is helping. She even felt so depressed that she started drinking heavily in the past couple of months. The doctor wants to try imipramine; however, since this drug is known to undergo an extensive first-pass effect, he orders a hepatic function panel before prescribing it, given the patient's recent history of alcohol use. What is the rationale for the doctor's decision? (A) In the presence of hepatic dysfunction, drugs with a high first-pass metabolism reach high systemic concentrations (B) The results of the hepatic function panel may reveal a particular susceptibility to the drug (C) Bioavailability of imipramine is increased by the fraction of drug removed by the first pass (D) The drug is more rapidly metabolized by the liver when hepatic aminotransferase levels are elevated (E) Solubility of the drug is affected in the face of hepatic damage
*The answer is A.* First-pass metabolism simply means passage through the portal circulation before reaching the systemic circulation. In the face of liver dysfunction, drug levels may reach higher concentrations. A hepatic function panel is generally not used to deduce a patient's susceptibility to the drug. Bioavailability of drugs is decreased, not increased by the fraction removed after the first pass through the liver. Drugs are usually less rapidly metabolized when hepatic enzymes are elevated (which indicates hepatic dysfunction). Solubility of drugs has nothing to do with hepatic damage.
Stimulation of liver microsomal enzymes can: a) Require the dose increase of some drugs b) Require the dose decrease of some drugs c) Prolong the duration of the action of a drug d) Intensify the unwanted reaction of a drug
*The answer is A.* If liver microsomal enzymes are stimulated, a dose increase is required.
A patient presents with an overdose of acidic Aspirin. The drug ____ can be given to ____ the pH of the urine and trap the Aspirin, preventing further metabolism. a) NaHCO3; Increase b) NaHCO3; Decrease c) NH4Cl; Increase d) NH4Cl; Decrease
*The answer is A.* In order to prevent the reabsorption of a drug, the drug must be in its ionized from. An acidic drug is in its ionized form when the pH is higher than its pKa. Therefore, the pH of the urine, must increase using a basic solution NaHCO3.
A 31-year-old man is brought to the emergency department complaining of dyspnea. He has a history of asthma and has had multiple asthma attacks requiring intubation for airway maintenance. He is noncompliant with his medications prescribed for this condition. Physical examination reveals a young man in acute distress. His room air oxygen saturation is 87%. In addition to administration of oxygen, immediate drug administration of albuterol should be administered by which of the following routes? (A) Inhalation (B) Intranasal puff metered dose (C) Subcutaneous (D) Sublingual (E) Topical
*The answer is A.* Inhalation provides rapid delivery of a drug across a large surface area of the respiratory tract and is the route of administration of choice in a patient with an airway disease such as asthma. Inhaled albuterol is commonly administered in this manner. (B) Intranasal puff metered dose would only deliver a small amount of drug to the patient and would not be recommended in this acutely ill patient (C) Subcutaneous administration is a slow route of administration and is not preferred in this acutely ill patient. (D) Sublingual, although allowing the medication to enter the circulation would be less preferred than the inhalation route in this acutely ill patient. (E) Topical administration would only achieve a local effect of the drug and is contraindicated in this acutely ill patient.
A new drug, drug A, undergoes a series of Phase I metabolic reactions before its metabolites ultimately are eliminated. Which statement best describers the characteristic of drug A, or the role of Phase I reactions in its metabolism or actions? A. Complete metabolism of drug A by Phase I reactions will yield products that are less likely to undergo renal tubular reabsorption B. Drug A is a very polar substance C. Drug A will be biologically inactive until it is metabolized D. Phase I metabolism of drug A involves conjugation, as with glucuronic acid or sulfate E. Phase I metabolism of drug A will increase its intracellular access and actions
*The answer is A.* Phase I metabolic reactions generally convert very nonpolar drug into more polar metabolites. Among other things, polar metabolites of drugs in general are less likely to undergo tubular reabsorption. We can generalize by saying that Phase I reactions play a role in forming metabolites that are "more easily excreted."
Which of the following is a phase II drug-metabolizing reaction ? (a) Acetylation (b) Deamination (c) Hydrolysis (d) Oxidation (e) Reduction
*The answer is A.* Phase II reactions are conjugation reactions ex. acetylation.
A 3-year-old is brought to the emergency department having just ingested a large overdose of diphenhydramine, an antihistaminic drug. Diphenhydramine is a weak base with a pKa of 8.8. It is capable of entering most tissues, including the brain. On physical examination, the heart rate is 100/min, blood pressure 90/50 mm Hg, and respiratory rate 20/min. Which of the following statements about this case of diphenhydramine overdose is most correct? (A) Urinary excretion would be accelerated by administration of NH4Cl, an acidifying agent (B) Urinary excretion would be accelerated by giving NaHCO3, an alkalinizing agent (C) More of the drug would be ionized at blood pH than at stomach pH (D) Absorption of the drug would be faster from the stomach than from the small intestine (E) Hemodialysis is the only effective therapy
*The answer is A.* Questions that deal with acid-base (Henderson-Hasselbalch) manipulations are common on examinations. Since absorption involves permeation across lipid membranes, we can in theory treat an overdose by decreasing absorption from the gut and reabsorption from the tubular urine by making the drug less lipid-soluble. Ionization attracts water molecules and decreases lipid solubility. Diphenhydramine is a weak base, which means that it is more ionized when protonated, ie, at acid pH. Choice C suggests that the drug would be more ionized at pH 7.4 than at pH 2.0, which is clearly wrong. Choice D says (in effect) that the more ionized form is absorbed faster, which is incorrect. A and B are opposites because NH4Cl is an acidifying salt and sodium bicarbonate an alkalinizing one. (From the point of view of test strategy, opposites in a list of answers always deserve careful attention.) E is a distracter. Because an acid environment favors ionization of a weak base, we should give NH4Cl. The answer is A. Note that clinical management of overdose involves many other considerations in addition to trapping the drug in urine; manipulation of urine pH may be contraindicated for other reasons.
A drug that binds to a receptor and produces a biological response that mimics the response to the endogenous ligand is known as (A) Agonist (B) Antagonist (C) Functional antagonist (D) Partial agonist (E) Partial antagonist
*The answer is A.* The definition of an ago-nist is the biologic response produced by a drug bind-ing to its receptor. For example, the α-adrenergic agonist phenylephrine when it binds to its receptor produces responses similar to the endogenous ligand. (B) Antagonists are drugs that decrease the actions of another drug or the endogenous ligand. (C) Functional antagonists may act at a separate receptor and oppose those effects of the agonist. (D) Partial agonists have activities somewhere between the full agonist and no agonistic activity. (E) Partial antagonists have activities somewhere between the full antagonist and no antagonistic activity.
A 79-year-old man with end-stage Alzheimer's disease and dysphagia is taking multiple medications. Physical examination reveals xerostomia and a limited gag reflex. Which of the following routes of medication administration would provide the lowest serum drug concentration? (A) Enteral (B) Intramuscular (C) Intrathecal (D) Intravenous (E) Transdermal
*The answer is A.* This patient has dysphagia and Alzheimer's disease. These conditions would make drug administration by mouth difficult and limit direct absorption via the stomach. This route of drug administration would give the lowest serum drug concentrations. (B) Intramuscular administration, although painful for the patient, would give acceptable serum drug concentrations. (C) Intrathecal administration would give acceptable therapeutic drug concentrations but would be limited to CNS disease states. (D) Intravenous administration would provide medications via vein and therapeutic drug concen-trations. It could be used for various medications. (E) Transdermal administration applies medications to the skin and could achieve therapeutic drug concentrations.
The following are excreted faster in basic urine (a) Weak acids (b) Strong acids (c) Weak Bases (d) None of the above
*The answer is A.* Weak acids are ionized in basic urine, so they are excreted faster.
Alkalinization of urine hastens the excretion of (a) Weakly basic drugs (b) Weakly acidic drugs (c) Strong electrolytes (d) Nonpolar drugs
*The answer is B.* Alkalinization of urine hastens the excretion of weak acids because they are highly ionized at basic pH.
A medical student is doing a summer research project evaluating the percentage of drug absorbed orally in a mouse model. Several characteristics of the agents are evaluated such as acid/base status, solubility, and size of side chains. Characteristics of the studied agent that would be best absorbed following oral administration in the tested mice would most likely include (A) Bulky charged side chains (B) Lipid solubility (C) Strong acid (D) Strong base (E) Water solubility
*The answer is B.* Although oral administration of a pharmacologic agent is convenient and economical, the drug must possess several characteristics for maximal absorption. In the stomach, drugs that are lipid soluble and that are weak acids can be readily absorbed. In the small intestine, drugs that are either weak acids or weak bases are able to be absorbed. (A) Medications with bulky side chains are not well absorbed following oral administration. (C) Strong acids are not well absorbed following oral administration. (D) Strong bases are not well absorbed following oral administration. (E) Water solubility can affect absorption rates of orally administered medications.
Glucuronidation reactions (A) Are considered phase I reactions (B) Require an active center as the site of conjugation (C) Include the enzymatic activity of alcohol dehydrogenase (D) Located in mitochondria are inducible by drugs (E) Require nicotinamide adenine dinucleotide phosphate (NADPH) for the enzymatic reaction
*The answer is B.* Glucuronidation reactions, which are considered phase II reactions, require an active center (a functional group) as the site of conjugation. Phase I reactions are biotransformation reactions, not conjugation reactions. Alcohol dehydrogenase is an example of a phase I reaction. Phase II reactions' enzymes are located in the endoplasmic reticulum, not mitochondria. Nicotinamide adenine dinucleotide phosphate (NADPH) is required for aromatic hydroxylation, an example of a phase I reaction.
A 15-year-old boy who has diabetes and is insulin dependent is brought to the emergency department after collapsing at a baseball game. His blood sugar is 463 mg/dL by finger stick. Which of the following routes of administration would be most efficacious for medications to bring the blood sugar down? (A) Intramuscular (B) Intravenous (C) Oral (D) Subcutaneous (E) Sublingual
*The answer is B.* Insulin (as most drugs) needs to enter the bloodstream for maximal effect; IV infusion will result in the fastest and highest peak blood insulin concentration. There are many formulations of insulin for intramuscular or subcutaneous injection, but even the fastest have no effect until the insulin reaches the systemic blood circulation. There is no way to make insulin absorption into the blood from intramuscular or subcutaneous injection faster than injecting directly into the blood. The same can be said for inhaled and sublingual insulin preparations. (A) Intramuscular insulin can be given in rapidly acting formulations, but even this is not as fast as IV insulin. (C) Insulin given orally would be broken down and rendered ineffective by peptidases in the gut. (D) Subcutaneous insulin can be given in rapidly acting formulations, but even this is not as fast as IV insulin. (E) Insulin is not normally given sublingually, and sublingual absorption is slower than IV infusion.
A novel medication designed to treat lymphoma can be administered via injection or orally. If the drug is given orally, an estimation of the area under the curve for this dose may be represented by which of the following letters in the following figure? (A) Letter A (B) Letter B (C) Letter C (D) Letter D (E) Letter E
*The answer is B.* Letter B represents the area under the curve (AUC) for oral administration of this agent. Letter C represents the AUC for injection of this agent. The ratio of Letter B to Letter C is the bioavailability of this agent. (A) Letter A is the drug administered. (C) Letter C is the area under the curve for injection of this agent. (D) Letter D is the drug injected degradation curve plotted against time (E) Letter E is the drug given orally degradation curve plotted against time.
The addition of glucuronic acid to a drug: A. Decreases its water solubility. B. Usually leads to inactivation of the drug. C. Is an example of a Phase I reaction. D. Occurs at the same rate in adults and newborns. E. Involves cytochrome P450.
*The answer is B.* The addition of glucuronic acid prevents recognition of the drug by its receptor. Glucuronic acid is charged, and the drug conjugate has increased water solubility. Conjugation is a Phase II reaction. Neonates are deficient in the conjugating enzymes. Cytochrome P450 is involved in Phase I reactions.
Biotransformation of drugs is primarily directed to (a) Activate the drug (b) Inactivate the drug (c) Convert lipid soluble drugs into nonlipid soluble metabolites (d) Convert nonlipid soluble drugs into lipid soluble metabolites
*The answer is C.* Biotransformation of drugs is primarily directed to convert lipid soluble drugs into nonlipid soluble metabolites.
Conjugation is: a) Process of drug reduction by special enzymes b) Process of drug oxidation by special oxidases c) Coupling of a drug with an endogenous substrate d) Solubilization in lipids
*The answer is C.* Conjugation is the coupling of a drug with an endogenous substrate.
Conjugation of a drug includes the following EXCEPT: a) Glucoronidation b) Sulfate formation c) Hydrolysis d) Methylation
*The answer is C.* Conjugation of a drug includes the following except hydrolysis. Hydrolysis is a phase I reaction.
Which of the following statements is correct? a) Microsomal oxidation always results in inactivation of a compound b) Microsomal oxidation results in a decrease of compound toxicity c) Microsomal oxidation results in an increase of ionization and water solubility of a drug d) Microsomal oxidation results in an increase of lipid solubility of a drug thus its excretion from the organism is facilitated
*The answer is C.* Microsomal oxidation results in an increase of ionization and water solubility of a drug.
Which tissue has the greatest capacity to biotransform drugs? (a) Brain (b) Kidney (c) Liver (d) Lung (e) Skin
*The answer is C.* The liver has the greatest capacity to biotransform drugs.
Biotransformation of the drugs is to render them: a) Less ionized b) More pharmacologically active c) More lipid soluble d) Less lipid soluble
*The answer is D.* Biotransformation of the drugs is to render them less lipid soluble and more ionized for excretion.
A 27-year-old woman takes phenytoin to control focal seizures. Most of the phenytoin in her blood is plasma-protein bound, and only the free fraction is pharmacologically active. The free fraction must diffuse through many barriers to reach its site of action. Many characteristics influence a drug's ability to diffuse across biologic membranes. Which of the following possible drug characteristics would aid such diffusion? (A) Hydrophilicity (B) Large molecular size (C) Weak acid with a pKa of 7 (D) Weak base with a pKa of 7
*The answer is D.* Characteristics that aid diffusion across biologic membranes include hydrophobicity (uncharged, nonpolar) and small size. A weak base with a pKa of 7 at a pH of 7 would exist as half RNH2 and half RNH3. Increasing the pH to 7.4 means decreasing the [H⁺], so the equilibrium for the reaction RNH3⁺ → RNH2 + H⁺ would be shifted to the right. A base with a pKa of 7 then would be mostly in the RNH2 state (not ionized RNH3⁺ state) at physiologic pH. This uncharged state (RNH2) is conducive to diffusion across biologic membranes. (A) Hydrophobicity aids diffusion across membranes, not hydrophilicity. (B) Small molecular size, not large, aids diffusion across membranes. (C) A weak acid with a pKa of 7 would exist as half ionized RCOO⁻ and half un-ionized RCOOH. As pH increases, more RCOOH will give up their H⁺ to become RCOO⁻. At physiologic pH, 7.4, more of this compound would be in the ionized RCOO⁻ state than in the uncharged RCOOH. Charges and polarity hinder a molecule's ability to diffuse across biologic membranes.
Which of the following statements is most correct regarding the termination of drug action? (A) Drugs must be excreted from the body to terminate their action (B) Metabolism of drugs always increases their water solubility (C) Metabolism of drugs always abolishes their pharmacologic activity (D) Hepatic metabolism and renal excretion are the two most important mechanisms involved (E) Distribution of a drug out of the bloodstream terminates the drug's effects
*The answer is D.* Hepatic metabolism and renal excretion are the two most important mechanisms involved in the termination of drug action. Note the "trigger" words ("must," "always") in choices A, B, and C. Some drugs are metabolized in the body to terminate their action. During metabolism, drugs tend to be converted to a more water-soluble form for excretion and their pharmacologic activity may be abolished, but this is not always the case. For example, acetaminophen becomes metabolized and turns into its active state.
A patient presents with an overdose of alkaline Codeine. The drug ____ can be given to ____ the pH of the urine and trap the Codeine, preventing further metabolism. a) NaHCO3; Increase b) NaHCO3; Decrease c) NH4Cl; Increase d) NH4Cl; Decrease
*The answer is D.* In order to prevent the reabsorption of a drug, the drug must be in its ionized from. A basic drug is in its ionized form when the pH is lower than its pKa. Therefore, the pH of the urine, must decrease using an acidic solution NH4Cl.
Induction of drug metabolizing enzymes involves (a) A conformational change in the enzyme protein to favor binding of substrate molecules (b) Expression of enzyme molecules on the surface of hepatocytes (c) Enhanced transport of substrate molecules into hepatocytes (d) Increased synthesis of enzyme protein
*The answer is D.* Induction of drug metabolizing enzymes involves increased synthesis of enzyme protein.
A 59-year-old man is going to undergo a prostate needle biopsy by his urologist. As a preparation for the procedure, he is required to take a fleet enema per rectum and a one time dose of ciprofloxacin 500 mg prior to the procedure. He has a prior medical history of diabetes mellitus, which is controlled with diet. Administration of the medication results in a peak plasma concentration of 20 μg/mL. What is the apparent volume of drug distribution? (A) 0.5 L (B) 1 L (C) 5 L (D) 15 L (E) 25 L
*The answer is E.* The volume of distribution is calculated by dividing the total amount of drug in the body by the plasma concentration of the drug. In this case, Vd = 500 mg ciprofloxacin/20 g/mL, which is the peak plasma concentration. Thus, the volume of distribution of ciprofloxacin is 25 L.
You are reviewing the data from several meta-analyses that addressed the most common causes of adverse or otherwise excessive effects of prescription drugs in young adults and in the elderly (>60 years of age). Interactions between multiple drugs were not considered. Which variable would you find to be decreased, and be the most common general cause of these problems, in the elders? a. Body fat content b. Lean body mass c. Liver function d. Renal function/clearance e. Plasma albumin levels
*The answer is D.* Most excessive and adverse effects from a single drug occur because of declines in renal excretory function. It affects drugs that are eliminated without prior metabolism, those for which metabolic inactivation plays a relatively small role in elimination, and those drugs that form one or more active metabolites. Declines of hepatic function clearly occur in advanced age, whether in the presence or absence of other factors that might impair hepatic drug metabolism, but that does not seem to account for the majority of cases of excessive drug effects. Body fat content tends to rise, not decrease, with age (a).
A 69-year-old woman is being treated in the intensive care unit for presumed staphylococcal sepsis. To avoid problems with possible resistance, she is empirically given IV vancomycin while waiting for the culture results to come back. Vancomycin is a renally excreted drug. The patient's routine laboratory work-up reveals a creatinine value of 3.2, indicating acute renal failure. What specific considerations will have to be made with regard to adjustments of the prescribed medication? (A) She will have to be switched to an oral (per nasogastric tube) vancomycin preparation (B) The patient will need to be water restricted to decrease the volume of distribution (C) No changes to the current regimen will be made because the condition of the patient is life-threatening and the drug needs to be administered regardless (D) The dose of vancomycin will need to be reduced because of increased accumulation (E) Dosage adjustments will have to be made because the patient is currently ventilated
*The answer is D.* Since vancomycin is cleared by the kidneys, renal functional status needs to be considered when prescribing such a drug, because it may accumulate and produce undesirable toxic side effects. Switching from the vancomycin to an oral preparation will reduce its bioavailability. There is no indication that the patient is in the state of increased volume of distribution (such as edema), and water restriction will not have a noticeable effect on apparent volume of distribution. Changes to the current regimen are necessary because of the patient's acute renal failure, and this has to be done regardless of the urgency of the situation. The fact that the patient is being ventilated may indicate that she needs extra hydration because of increased insensible losses, but this has nothing to do with her vancomycin dose directly.
A 27-year-old man with HIV disease and hepatic insufficiency presents to his primary care physician complaining of rectal pain and bleeding with bowel movements. Physical examination reveals several internal and external hemorrhoids. The patient would like to avoid surgical therapy for this condition. Which of the following routes of drug administration would be preferred in this patient? (A) Enteral (B) Intramuscular (C) Intravenous (D) Rectal (E) Transdermal
*The answer is D.* This patient has hemorrhoids, and a topical route of administration of medication is preferred. This route avoids the hepatic first pass effect so the patient's liver insufficiency would not likely be problematic with this route of administration. (A) Enteral route administration will be un-likely to achieve an adequate therapeutic response in a patient with hemorrhoids. (B) Intramuscular route administration is an ineffective therapy for rectal diseases. (C) Intravenous administration is an ineffective therapy for rectal diseases such as hemorrhoids. (E) Transdermal administration achieves systemic effects through systemic absorption of medication. It is not effective for internal hemorrhoids.
A drug, given as a 100-mg single dose, results in a peak plasma concentration of 20 μg/mL. The apparent volume of distribution is (assume a rapid distribution and negligible elimination prior to measuring the peak plasma level): A. 0.5 L. B. 1 L. C. 2 L. D. 5 L. E. 10 L.
*The answer is D.* Vd = D/C, where D = the total amount of drug in the body, and C = the plasma concentration of drug. Thus, Vd = 100 mg/20 mg/mL = 100 mg/20 mg/L = 5 L.
Concerning renal drug excretion: A) almost all drugs are filtered by the glomerulus B) a lipid-soluble, filtered drug will likely be reabsorbed by passive diffusion C) pH partitioning (the drug is ionized at the urinary pH) enhances excretion D) weak acids are excreted faster in alkaline urinary pH E) all of the above
*The answer is E.* Almost all drugs are filtered by the glomerulus. Lipid-soluble, filtered drugs are more likely to be reabsorbed by passive diffusion, while ionized drugs are more likely to be excreted. Weak acids are excreted faster in alkaline urinary pH, whereas weak bases are excreted faster in acidic urinary pH.
Based on the relation between the degree of ionization and the solubility of a weak acid, the drug aspirin (pKa 3.49) will be most soluble in urine at: (a) pH 1.0 (b) pH 2.0 (c) pH 3.0 (d) pH 4.0 (e) pH 6.0
*The answer is E.* Weak acids are ionized in basic urine, so they are excreted faster. Therefore, asipirin will be more soluble at the pH of 6.0.
