The pharmacokinetics of butorphanol nasal spray, with and without the coadministration of metoclopramide, were studied in 24 healthy women. In this crossover study all volunteers received 3 treatments: a single, 1-mg dose of butorphanol nasal spray, a single, 10-mg oral dose of metoclopramide, and a combination of a single, 1-mg dose of butorphanol nasal spray and a single, 10-mg oral dose of metoclopramide. There was at least a one-week washout period between sessions. Serial blood samples were collected and plasma samples analyzed using a validated radioimmunoassay to determine the concentration of butorphanol, or a high-performance liquid chromatography/ultraviolet procedure was used to determine the concentration of metoclopramide. There were no statistically significant differences in the pharmacokinetic parameters, Cmax, tmax, AUC, and t1/2, for butorphanol with or without metoclopramide. Similarly, except for a delay in tmax of metoclopramide with coadministration of butorphanol, the pharmacokinetic parameters of metoclopramide were not significantly different between two treatments. Thus, the pharmacokinetics of both butorphanol and metoclopramide were not significantly altered when administered in combination. The incidence of nausea/vomiting after butorphanol administration was substantially reduced by coadministration of metoclopramide. Based on the pharmacokinetic and safety results, it can be concluded that butorphanol nasal spray and metoclopramide can be administered in combination without altering the dose regimen of either drug.