Pharmacokinetics of diphenhydramine and a demethylated metabolite following intravenous and oral administration

Journal of Clinical Pharmacology
G T BlydenR I Shader

Abstract

Ten healthy volunteers received a single 50-mg dose of diphenhydramine (DP) hydrochloride intravenously and orally on two separate occasions. Kinetics of DP and a major demethylated metabolite (DMDP) were determined from multiple plasma samples drawn during a 24- to 48-hour period after dosage. Modification of a gas chromatographic (GC) technique allowed simultaneous quantitation of DP and DMDP. Mean kinetic variables for DP after intravenous (IV) dosage were: volume of distribution, 4.5 L/kg; elimination half-life, 8.4 hours; clearance, 6.2 mL/min/kg. After oral DP administration, a peak plasma level of 66 ng/mL was reached 2.3 hours after dosage. Systemic availability was 72%, nearly identical to the predicted estimate (71%) based on clearance of IV DP relative to hepatic blood flow. Appearance of the metabolite, DMDP, mirrored disappearance of DP; the area under the plasma concentration-time curve (AUC) for DMDP was highly correlated (r = .79, P less than .05) with a clearance of IV DP. However, metabolite AUC was significantly higher after oral as opposed to IV DP (218 vs 145 hr-ng/mL, P less than .05). Because DP and DMDP elute nearly identically on standard GC systems, methodologic modifications are needed to resolve them...Continue Reading

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