A multi-center study to evaluate the pharmacokinetic and clinical interactions between alprazolam and imipramine
Tóm tắt
The results of this study document the safety of co-administering alprazolam at doses up to 4 mg per day to patients already receiving imipramine. Although a pharmacokinetic interaction was observed by both a traditional analysis approach and a population analysis approach resulting in a significant increase in imipramine and desipramine plasma concentrations, no adverse pharmacodynamic effects were found in behavioral measurements or the incidence and severity of side effects. The ability of population pharmacokinetic analysis to provide insight in interpreting the results obtained from the traditional pharmacokinetic evaluation provide further support for the use of performing population pharmacokinetic analysis of data collected during clinical studies.
Tài liệu tham khảo
L. Ereshefsky, B.G. Wells, R.L. Evans, E.J. Antal, R.B. Smith, A.L. Richards, L.J. Birkhimer, S.R. Saklad, M.W. Jann, and C.J.G. Perry, Pharmacokinetic and pharmacodynamic interactions between alprazolam and imipramine,J. Clin. Pharmacol. (1988), submitted.
T.H. Grasela, E.J. Antal, L. Ereshefsky, B.G. Wells, R.L. Evans, and R.B. Smith, An evaluation of population pharmacokinetics in therapeutic trials. Part II. Detection of a drug-drug interaction,Clin. Pharmacol. Ther. 42:433 (1987).
B.G. Wells, R.L. Evans, L. Ereshefsky, E.J. Antal, F. Lobek, W.N. Rawls, G. Hamann, J. Grimmig, and R.B. Smith, Clinical outcome and adverse effect profile associated with concurrent administration of alprazolam and imipramine,J. Clin. Psych. 49: 394 (1988).
S.L. Beal and L.B. Sheiner, “NONMEM User's Guides,” NONMEM Project Group, University of California, San Francisco (1989).
C.R. Rao, “Linear Statistical Inference and its Application,” John Wiley & Sons, New York, pp. 347–352 (1965).