Gender: a possible determinant in dosing of dermatologic drugs--an overview.
The role of gender in pharmacokinetics could play a significant role in tailoring HIV and other drug regimens. Here we investigate sex as a factor in saquinavir pharmacokinetics. The HIV-positive women who use saquinavir in combination with other protease inhibitors frequently demonstrate higher saquinavir concentrations than their male counterparts. The majority of the data indicates that the root of women's higher saquinavir concentrations is not inherent to their gender. Rather, extenuating factors associated with HIV play a prominent role in the observed difference between men and women's pharmacokinetic parameters. The source of observed differences in saquinavir pharmacokinetics could not be definitively traced to CYP3A, the enzyme responsible for saquinavir's metabolism or drug transporters. Hormonal changes associated with HIV infection together with concurrent use of other protease inhibitors could help explain development of sex differences. These findings can be used to further investigate when and why gender-based differences in saquinavir pharmacokinetics exist and possible future dosage and therapy considerations. Our knowledge of gender-related pharmacokinetics should be extended for other systemic drugs in dermatology.
Modjtahedi
Bobeck S
BS
Department of Dermatology, School of Medicine, University of California, San Francisco, CA, USA.
Modjtahedi
Sara P
SP
Maibach
Howard I
HI
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D002986:Clinical Trials as Topic; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003879:Dermatologic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D008099:Liver / Q000201:enzymology; D008297:Male; D019258:Saquinavir / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012727:Sex Characteristics
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D003879:Dermatologic Agents; D017320:HIV Protease Inhibitors; D003577:Cytochrome P-450 Enzyme System; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D019258:Saquinavir