Disposition and miotic effects of oral alfentanil
Boys high top soccer cleats evan D. Kharasch MD, PhD1, Christine Hoffer CCRC1, Alysa Walker BS1 and Pamela Sheffels BS1Correspondence: Evan D. Kharasch, MD, PhD, Department of Anesthesiology, University of Washington, Box 356540, 1959 NE Pacific, RR442, Seattle, WA 98195.
Received 12 August 2002; Accepted 7 November 2002.
Top of pageAbstractBackground and Objectives: Systemic clearance of the opioid alfentanil after intravenous administration is an excellent in vivo probe for hepatic cytochrome P4503A (CYP3A) activity and drug boys high top soccer cleats interactions. Alfentanil effect (miosis) is a surrogate for plasma alfentanil concentrations, and alfentanil effect kinetics may be a suitable noninvasive probe for hepatic CYP3A. Oral boys high top soccer cleats alfentanil might be a probe for firstpass CYP3A activity; however, it is not used clinically, and oral alfentanil disposition is unknown. This investigation evaluated the disposition and miotic effects of oral alfentanil.
Methods: Ten healthy volunteers were studied in a doseescalation fashion, receiving 23, 30, 43, and 75 g/kg oral alfentanil on different days. Darkadapted pupil diameter was measured at the time of venous blood sampling. Alfentanil was quantified by liquid chromatographymass spectrometry. Plasma concentrations of alfentanil and pupil diameter change versus time data were analyzed by noncompartmental modeling.
Results: Alfentanil was rapidly absorbed (time to maximum concentration [Tmax], 0.7 0.5 hour). Mean values for area under the plasma concentrationtime curve extrapolated to infinity (AUC) (27 14, 38 22, 57 31, and 105 59 ng h mL1) and maximum concentration (16 8, 23 16, 31 18, and 50 22 ng/mL) were linear with dose, although there was considerable interindividual variability. Tmax, elimination halflife (1.0 0.2 hours), total body clearance after oral administration (20 18 mL kg1 min1), and dosenormalized AUC boys high top soccer cleats were independent of dose. Dosedependent alfentanil disposition was mirrored by commensurate changes in clinical effect, although miosis was variable and not detectable in all subjects at the lowest dose. Mean miosis AUC (AUEC) and peak miosis were logdose linear. Effect halflife (1.3 0.9 hours) was similar to plasma nike indoor soccer halflife.
Conclusion: Oral alfentanil is rapidly absorbed, exhibits linear and doseindependent kinetics, and undergoes substantial firstpass metabolism. Oral alfentanil may be a suitable probe for firstpass CYP3A activity. Alfentanil effect (miosis) may be an acceptable surrogate for plasma alfentanil concentrations. Oral alfentanil effect may be a noninvasive surrogate for conventional pharmacokinetics. Further studies are warranted to determine whether nike indoor soccer oral alfentanil and alfentanil effect kinetics may be a suitable noninvasive in vivo probe for firstpass CYP3A activity boys high top soccer cleats.