Disposition and clinical side effects of pentazocine when administered during day and night

The question of possible circadian rhythm upon administration of 6,11-dimethyl-2,6-methano-3-(3-methyl-2-butenyl)-1,2,3,4,5,6-hexahydro-3- benzazocin-8-ol (pentazocine, Talwin) (which was found to exist in beagle dogs) was studied in eight healthy, male volunteers. Six of the subjects resided in the USA, and two subjects joined the study group the night before the morning experiment from Europe. All blood concentration-time data after i.v. injection starting between 8-9 a.m. and 8-9p.m., respectively, were best fit by biexponential curves. The derived pharmacokinetic parameters were essentially identical to those reported in the literature. Overall, no statistically significant differences were found for any of the parameters between the day and night study. However, the two volunteers from Europe demonstrated significant differences in the volume of distribution. Although the sample number is too small to draw final conclusions, it indicates the need for further studies regarding possible influences by offsetting the biologic clock, or "jet-lag" on drug disposition. No differences were found in clinical effects between the day and night study. However, all clinical effects were significantly more pronounced after the first than after the second dose, regardless of time of administration.