VERAPAMIL
Verapamil is used to treat high blood pressure and to controlangina (chest pain). Verapamil undergoes O-demethylation,N-dealkylation, and N-demethylation to a number of differentmetabolites via the cytochrome P450 enzyme system. The followingtable reports typical pharmacokinetic data for the drugVerapamil
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VERAPAMIL
Verapamil is used to treat high blood pressure and to controlangina (chest pain). Verapamil undergoes O-demethylation,N-dealkylation, and N-demethylation to a number of differentmetabolites via the cytochrome P450 enzyme system. The followingtable reports typical pharmacokinetic data for the drugVerapamil
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BIOAVAILABILITY (ORAL) (%)
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URINARY EXCRETION (%)
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BOUND IN PLASMA (%)
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CLEARANCE (mL/min/kg)
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VOL. DIST. (L/kg)
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HALF-LIFE (hours)
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22 ± 8
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<3
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90 ± 2
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15 ± 6
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5.0 ± 2.1
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4.0 ± 1.5b
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↓ LD
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↓ LD
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? LD
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? LD
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? LD
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- Is Verapamil a low, medium or high extraction ratio drug?Why?
- Predict the changes in clearance, half-life, and volume ofdistribution in patients with Liver Disease (LD). Notethat one of the effects of LD is to slow blood flow through theliver as well as to lower metabolism efficiency.
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Clearance
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Vol. Distr.
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Half-live
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dec, equilibrium, inc
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dec, equilibrium, inc
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dec, equilibrium, inc
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- Calculate exposure (AUC mg/L/hr) following a 100 mg oral doseof Verapamil hydrochloride (MW 491 kD) to a 58-year-old female (62kg) patient.
- What IV-bolus dose should you administer to obtain the sameexposure?
- What is the plasma concentration in µg/L 4 hours from theadministration of a 100 mg tablet verapamil-hydrochloride? (Assume1st order absorption, ka = 2 hrs-1 and the same femalepatient, 62kg).
- How many microgram of drug are in the body of this patient att=4 hours?
- Calculate metabolic clearance in the same subject.
LORAZEPAM
The following table reports pharmacokinetic data for the drugLorazepam. It is cleared primarily by glucuronidation byUGT2B7 and UGT2B. In LD and RD patients the fraction ofdrug bound to plasma protein decreases.
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BIOAVAILABILITY (ORAL) (%)
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URINARY EXCRETION (%)
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BOUND IN PLASMA (%)
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CLEARANCE (mL/min/kg)
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VOL. DIST. (L/kg)
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HALF-LIFE (hours)
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93 ± 10
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<1
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91 ± 2
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0.61 ± 0.01a
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1.3 ± 0.2b
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14 ± 5
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↓ LD, RD
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? LD, RD
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? LD, Neo, RD
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- Is Lorazepam a low, medium or high extraction ratio drug?Why?
- Predict the changes in clearance, half-life, and volume ofdistribution in patients with Liver Disease (LD). Notethat one of the effects of LD is to slow blood flow through theliver as well as to lower metabolism efficiency.
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Clearance
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Vol. Distr.
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Half-live
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dec, equilibrium, inc
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dec, equilibrium, inc
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dec, equilibrium, inc
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- Calculate plasma water clearance for lorazepam inmL/min/kg.
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- What is the plasma concentration in µg/L 4 hours from theadministration of a 100 mg tablet verapamil-hydrochloride? (Assume1st order absorption, ka = 2 hrs-1 and the same femalepatient, 62kg).
- How many microgram of drug are in the body of this patient att=4 hours?
- Calculate metabolic clearance in the same subject.
