Aims Gender differences are known to occur in the pharmacokinetics of many drugs. Mechanisms may include differences in body composition, body weight, cardiac output, hormonal status, and use of different co-medications. Recently subtle gender-dependent differences in cytochrome P450 (CYP) 3A-dependent metabolism have been demonstrated. Buprenorphine N-dealkylation to norbuprenorphine is primarily performed by CYP3A. We therefore asked whether gender-dependent differences occur in the pharmacokinetics of buprenorphine. Methods A retrospective examination was made of control (buprenorphine/naloxone-only) sessions from a number of drug interaction studies between buprenorphine and antiretroviral drugs. Twenty males and eleven females were identified who had a negative cocaine urine test prior to participation in the control session and were all on the same maintenance dose (16/4 mg) of sublingual buprenorphine/naloxone. Pharmacokinetic data from their control sessions (buprenorphine/naloxone only) were sorted by gender and compared using the two-sample t-test. Results Females had significantly higher area under the plasma concentration curve (AUC) and maximum plasma concentrations for buprenorphine, norbuprenorphine and norbuprenorphine-3-glucuronide. AUCs relative to dose per body weight and surface area were significantly higher for only norbuprenorphine. AUCs relative to lean body mass were, however, not significantly different. Conclusions Gender-related differences exist in the pharmacokinetics of buprenorphine; differences in body composition appear to have a major impact; differences in CYPA-dependent metabolism may also contribute.

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though many of these monopole excitations involve muonic states with n > 3 and low orbital angular momentum, they may be detected by ycoincidence techniques. We feel that the method employed by Jenkins, Powers, and Kurselman 5 would not be sufficiently sensitive for the cases considered here.A complete and detailed discussion of all of the resonances investigated is in preparation.The extensive numerical calculations carried out in support of this investigation were done on the Honeywell GE 635 computer at the University of Kansas Computation Center. tWork supported in part by the U. S. Atomic Energy Commission. •National Science Foundation Trainee. 1 J. Hufner, Z. Phys. 190, 81 (1966). 2 E. M. Henley and L. Wilets, Phys. Rev. Lett. 2£, 1389 (1968). 3 M. K. Sundaresan and V. Srinivasan, Phys. Rev.The Utah group has previously published evidence indicating an anomalous zenith-angle dependence for cosmic-ray muons observed at depths in excess of 2xl0 5 g/cm 2 . 1 " 3 In this Letter, we present a new analysis based on an order of magnitude more data than were then available, The methods of analysis have been revised in such a way that the anomaly is more visible and the result is almost completely independent of the parameters of cosmic-ray phenomenology. In addition, vertical muon intensity measurements by Cassiday, Gilbert, and White 4 provide an absolute depth inter calibration which permits inclusion of vertical intensity data from a world survey in the analysis. When this is done, meaningful results may be extracted to a slant depth Lett. 21_, 1509 (1968). 4 J. Hufner, Phys. Lett. 25B, 189 (1967).

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In principle, there exists a second invariant in the fourth-order derivatives of~. However, in a system with translational invariance this term is identical with that given in (1).