Relative bioavailability of trimeprazine tablets investigated in man using HPLC with electrochemical detection

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Abstract
The stability, partition coefficient, plasma protein binding, red blood cell distribution, and whole blood concentrations of trimeprazine were investigated. Trimeprazine solution was stable for 6 months at −20 °C and 3.5 months at 40 °C. In whole blood trimeprazine was stable for 5 weeks at −20 °C., 24 h at 4 °C., 4h at 25 °C and 1 h at 37 °C. The apparent hexane-water partition coefficient varied from 1.50 (at pH 4.83) to over 100 (at pH 10.54). The fraction bound to plasmaprotein exceeded 0.9 as estimated by equilibrium dialysis with correction for volume shift. The mean plasma/red blood cell concentration ratio was 1.17 and the mean red blood cell/plasma distribution coefficient was 8.65. Six healthy adult males received single 5 mg doses of trimeprazine in a syrup (5 mg in 10 ml) and tablets with at least two weeks between doses. Blood was collected for 48 h. The mean (±s.e.m.) times for peak blood concentrations were 3.5 ± 0.22 h for the syrup and 4.5 ± 0.43 h for the tablets. There were no significant differences in Cmax values. The overall mean (±s.e.m.) terminal phase half-life was 4.78 ± 0.59 h. Mean (±s.e.m.) areas under the concentration time curves from 0 to infinity (AUC∞) were 11.0 ± 1.99 ng h−1 ml−1 and 7.67 ± 1.05 ng h−1 ml−1 for syrup and tablets, respectively. The mean relative bioavailability for the tablets was approximately 70% with respect to the syrup.