Marihuana cigarettes containing 1.32%, 1.97%, and 2.54% delta 9-tetrahydrocannabinol (THC) were smoked by six experienced marihuana users at weekly intervals in a double-blind cross-over design under laboratory conditions. Puff duration, number of puffs taken, duration of inhalation holding, interval between puffs, and duration of smoking were recorded for each cigarette smoked. The portion of each cigarette remaining after smoking was weighed and analyzed to determine THC content. Subjective ratings of the "high" achieved and the heart rate acceleration induced by smoking the marihuana were measured. The plasma concentrations of THC and of its principle metabolite, 11-nor-delta 9-THC-9-carboxylic acid (9-carboxy THC), were determined by radioimmunoassay of blood samples drawn at frequent intervals for 6 hr. The results indicate that, irrespective of the potency of the marihuana, the pattern of smoking was much the same. The magnitude of the subjective high, heart rate acceleration, THC, and 9-carboxy THC plasma concentrations were proportional to potency. This dose response was particularly clear between the 1.32% and the 2.54% cigarettes. Peak plasma concentrations of THC consistently occurred 7 to 8 min after initiation of smoking and declined thereafter despite continued smoking for another 6 to 10 min. Peak subjective high and peak heart rate acceleration occurred several minutes after the end of smoking and at a considerable interval after maximal THC plasma concentrations were reached.

Fourteen normal male subjects were given either 60mg or 180mg of terfenadine suspension in a randomized two-way crossover study. Peak plasma concentrations of 1.544 +/- 0.726 (mean +/- S.D.) ng ml-1 were obtained in 0.786 h following the 60 mg dose and displayed an AUC or 11.864 +/- 3.369 ng h ml-1. Whereas peak plasma concentrations of 4.519 +/- 2.002 ng ml-1 in 1.071 +/- 0.514 h were obtained following the 180 mg dose. The AUC following the 180 mg dose was 44.341 +/- 22.041 ng h ml-1. When 60 mg of 14C terfenadine was given to six additional subjects, the peak plasma concentrations of 351 +/- 43 ng equivalents per ml were obtained in 1.67 +/- 0.41 h and the AUC was 2297.71 +/- 310.85 ng-equivalents h ml-1. This indicates that approximately 99.5 per cent of the terfenadine related material that is absorbed undergoes biotransformation. Urinary excretion of 14C accounted for 39.89 +/- 5.29 per cent of the dose while 60.58 +/- 2.44 per cent of the dose was recovered in the feces in twelve days. Thin-layer chromatographic (TLC) examination of fecal extracts showed only a trace of material chromatographing with terfenadine. This may indicate that the 14C present in the feces is not due to lack of absorption.

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