BIOPHARMACEUTIC AND PHARMACOKINETIC EVALUATION OF HYDROMORPHONE (ERYTHROCYTE PARTITIONING, PROTEIN-BINDING, SALIVA/PLASMA RATIO, CLINICAL EFFECTS).

摘要

Biopharmaceutic parameters of hydromorphone were investigated. Hydromorphone has an apparent partition co-efficient of 0.307, pka(,1) and pka(,2) of 8.096 and 9.472, respectively. The extent of serum protein binding is 7.8% and has an erythrocyte partitioning of 0.599 (fraction).;The bioavailability of hydromorphone after P.O. and rectal administration is 50.6 (+OR-) 29.8% and 33.4 (+OR-) 22.9%, respectively. Low plasma hydromorphone concentrations were observed after rectal administration of hydromorphone as compared to I.V. and P.O. administration. The Cmax normalized for 1 mg hydromorphone dose to 70 kg subject for I.V., P.O. and rectal routes of administration are 133.84 (+OR-) 116.99 ng/ml, 4.067 (+OR-) 1.794 ng/ml and 1.219 (+OR-) 0.688 ng/ml, respectively. The tmax after P.O. and rectal administration are 1.29 (+OR-) 0.24 h and 1.40 (+OR-) 0.77 h, respectively.;More side effects were experienced after I.V. administration of hydromorphone as compared to P.O. and rectal administration of hydromorphone. There was no signficant difference in the estimate of elimination half-life determined from saliva and plasma concentrations, thus indicating use of saliva hydromorphone concentration as a non-invasive technique in the estimation of elimination half-life of hydromorphone.;Pharmacokinetics of hydromorphone was studied after I.V., P.O. and rectal administration of hydromorphone to eight healthy male subjects using a cross-over Latin square design with a wash out period of two weeks. Hydromorphone has a short elimination half-life (2.363 (+OR-) 0.584 h) and a large volume of distribution (2.9 (+OR-) 1.309 l/kg).