PURPOSE: To evaluate the gender-specific effect on intravenous and oral cyclosporine (CsA) pharmacokinetics in healthy subjects.
METHODS: As part of an on-going study, the pharmacokinetic data of CsA was analyzed to evaluate the gender effect on disposition of cyclosporine in healthy subjects. A total of 9 female (F) and 11 male (M) subjects participated in the study. Each subject received oral doses of CsA (5 ㎎/㎏) and one intravenous dose of CsA (1.5 ㎎/㎏) in a fasted condition, with each dose separated by at least a one-week washout period. A total of 17 blood samples were collected for a 24-hour period, and whole blood concentrations of CsA were determined by an HPLC method with UV detection.
RESULTS: The mean systemic clearance (Cls) and apparent oral clearance (Cl/F) of CsA were significantly faster in F compared to M [For Cls, 283±47 ㎖/min/㎏ (F) vs. 222±32 ㎖/min/㎏ (M), p=0.0028, and for Cl/F, 825±279 ㎖/min/㎏ (F) vs. 627±90 ㎖/min/㎏ (M), p=0.0395]. The area under the curve (AUC) of Ⅳ CsA was smaller in F compared to M [5440±1045 ng.hr/㎖ (F) vs. 6813±893 ng.hr/㎖ (M), p=0.005], but when the AUC was adjusted for body weight, the differences disappeared (p=0.7). All other pharmacokinetic parameters between F and M were not significantly different.
CONCLUSION: This study shows that Cls and Cl/F of CsA in female subjects were significantly faster than those in male subjects, which is consistent with the results of other CYP3A substrates.
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