Effect of Single Dose Fluoxetine on Theophylline Serum Concentrations.
Fluoxetine has been previously reported to elevate plasma concentrations of several hepatically metabolized medications. Eight healthy male volunteers received intravenous aminophylline (approximately 6 mg kg(minus sign1)) on two occasions separated by 2 weeks. A 40-mg dose of oral fluoxetine was administered 8 h prior to the second administration of fluoxetine. Blood samples were collected and assayed for theophylline. Fluoxetine administration was not associated with any significant differences with respect to peak theophylline serum concentration, total body clearance, or half-life. Possible explanations include the fact that only a single dose of fluoxetine was administered and low fluoxetine serum concentrations were present at the time of aminophylline administration. The most likely explanation, however, is the fact that fluoxetine inhibits cytochrome P450 2D6 activity, whereas theophylline is predominately metabolized by cytochrome P450 1A2. In summary, a single 40-mg dose of fluoxetine failed to alter the plasma concentrations of theophylline when administered intravenously as aminophylline.
Mauro
Vincent F.
VF
College of Pharmacy, University of Toledo, Toledo, OH 43606 USA and Medical College of Ohio, Toledo, OH 43699, USA.
Mauro
Laurie S.
LS
Klions
Howard H.
HH