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Pharmacokinetics of Diphenhydramine and a Demethylated Metabolite Following Intravenous And Oral Administration
Author(s) -
Blyden Gershwin T.,
Greenblatt David J.,
Scavone Joseph M.,
Shader Richard I.
Publication year - 1986
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1986.tb02946.x
Subject(s) - pharmacokinetics , metabolite , chemistry , oral administration , volume of distribution , pharmacology , active metabolite , diphenhydramine , chromatography , medicine , histamine , biochemistry
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 < .05) with clearance of IV DP. However, metabolite AUC was significantly higher after oral as opposed to IV DP (218 vs 145 hr‐ng/mL , P < .05). Because DP and DMDP elute nearly identically on standard GC systems, methodologic modifications are needed to resolve them. Coelution of the two compounds could bias kinetic data based on plasma concentration presumed to be specific for intact DP .