High-pressure liquid chromatographic determination of promethazine plasma levels in the dog after oral, intramuscular, and intravenous dosage.

Plasma levels of promethazine were determined using a high-pressure liquid chromatographic procedure incorporating a fixed wavelength (254 nm) UV detector, following single 50-mg intravenous, intramuscular, and oral doses to two male dogs. Initial plasma promethazine concentrations following intravenous doses were 556 and 535 ng/ml in the two dogs. The subsequent decline in drug levels were satisfactorily described by a triexponential function. Peak promethazine levels of 76 and 64 ng/ml were obtained 0.5 hr following intramuscular doses. Peak levels for the oral doses were 10.6 and 11.0 ng/ml occurring 2 hr after dosing. The apparent biological half-life of promethazine, obtained from only 2-3 data points, varied from 8.5 to 27.7 hr. Areas under the promethazine plasma curves, compared to values obtained from intravenous doses between 0 and 24 hr, indicated that systemic availability of intact drug was 55-73% following intramuscular injection and 8.3-9.5% following oral administration.