Fluoxetine, a selective serotonin uptake inhibitorFluoxetine is a selective serotonin uptake inhibitor in man. Platelets harvested from subjects to whom jiuoxetine was administered (30 The pharmacology of fluoxetine* (Fig. I) has been studied extensively in animals. 9 , 13, 20, 21 It selectively inhibits serotonin uptake in rat brain synaptosomes 20 and platelets,13 prevents pchloroamphetamine-induced depletion of brain serotonin, 9 and appears to be without effects on the noradrenergic system. 20, 21 Its selectivity as an inhibitor of the serotonin uptake pump has Received for publication Oct. 12, 1977. Accepted for publication Dec. 22, 1977. generated considerable interest, and thus fluoxetine has been used as a pharmacologic tool for evaluating the physiologic role of the serotonergic system. There is also interest in using a drug of this type in clinical studies to help elucidate the role of serotonin in the pathophysiology of neuroendocrinologic and psychiatric disorders. We describe the clinical pharmacology of fluoxetine and its effects on the noradrenergic and serotonergic systems in man.

Fluoxetine (Li-ly 110140) caused a 63 percent inhibition of [3H]serotonin uptake into platelets obtained from normal volunteers to whom the drug was administered daily for 7 days. This dose had no effect on the usual pressor response produced by injections of norepinephrine or tyramine.

No abstract

A study of the effect of crystal size on the bioavailability of benoxaprofen, 2-[4-chlorophenyl]-alpha-methyl-5-benzoxazoleacetic acid, in man is reported. The technique utilized comparison of either the plasma concentrations or urine levels, resulting from administration of deuterium labeled (2H7) drug in solution coadministered with a test capsule formulation. Drug concentrations were determined by gas chromatography, and the ratio of labeled to unlabeled drug was obtained by gas chromatography mass spectrometry. Measurements following coadministration of labeled and unlabeled drug in solution established the absence of an isotope effect due to the presence of deuterium. The dry formulations consisted of either a 3.17--100 micron fraction (mean = 18.5 microns) or a 32--1000 micron fraction (mean = 610 microns) formulated with starch powder. The results in three subjects indicate an almost complete availability (0.95--0.98) of the small crystals as measured by comparison of either area under the plasma level curves or urine excretion (0.94--0.97) of labeled versus unlabeled drug measured to 168 hours. The larger crystals exhibited a lower availability as shown by plasma levels (0.41--0.46) or urine recovery (0.39--0.43). A higher dose of the large crystal formulation resulted in decreased relative availability with a fourfold dose dropping availability to 0.22 in a single subject.