[Pharmacokinetics and bioavailability of diphenhydramine in man]

By the presented study the relative bioavailabilities and some important pharmacokinetic parameters should be evaluated after oral application of a single-dose of three different diphenhydramine (DPH, 2-diphenylmethoxy-N,N-dimethylethylamine)preparations in a randomized, cross-over design to 12 healthy volunteers. Additionally, some simple pharmacodynamic measurements of the volunteer's vigilance were performed and the question whether a combination with 8-chlorotheophylline influences the pharmacokinetic and/or pharmacodynamic profile of DPH was investigated. As the test preparations (Benocten as a tablet = A, as a buffered solution = B) contained 50 mg of DPH-HCl, but the reference preparation (= C) only 31 mg of DPH-HCl (+ 23 mg 8-chlorotheophylline), the biometric-statistic calculations had to be done with and without dose correction. Bioequivalence of the preparations could only then be demonstrated when the calculations were done with dose corrections: without these corrections for the reference preparation significantly lower serum levels resulted which hardly can be considered sufficient for exerting a sleep-inducing effect. The addition of 8-chlorotheophylline recommended by some other authors for an enhanced sedative effect could not be substantiated by our results. Peak serum levels of 61 and 53 ng/ml, respectively, for the test preparations and 40 ng/ml for the reference preparation were reached after 2.0 to 2.5 h p.a.; elimination half-lives were between 4 and 6 h. A statistically significant positive correlation could be found for AUC (0-24 h) and the amount excreted in urine in the same period of time, as higher mean serum levels were correlated with higher amounts excreted renally.(ABSTRACT TRUNCATED AT 250 WORDS)