Fluoxetine (FL) is being used in neuropharmacology as a tool for studying various functional roles of serotoninergic neurons. Its kinetics was studied in rats, a species widely used in neurochemical studies, after IV (2.5-10 mg/kg) and oral (5-20 mg/kg) administration. When injected IV the drug followed apparent first-order kinetics up the 10 mg/kg dose. Its volume of distribution was large and total body clearance was relatively high compared to liver blood flow. The mean elimination half-lives (t1/2) of FL and its active metabolite norfluoxetine (NFL) were about 5 and 15 h, respectively. The mean blood:plasma concentration ratios of FL and NFL approached unity and plasma protein binding was 85-90% for both compounds. After oral doses the kinetics of FL were complex. At the lowest dose tested (5 mg/kg) the drug was efficiently extracted by the liver (extraction ratio about 60%), resulting in bioavailability of only about 38%. Plasma areas under the curve (AUC) of the metabolite were approximately the same as after IV injection of the same dose; consequently the metabolite-to-parent drug ratio after oral administration (about 5) was approximately twice that after IV injection of FL (about 2.5). At higher doses, however, the oral bioavailability (e.g. Cmax and AUC) appeared greater than expected, possibly because of transient saturation of FL first-pass metabolism in the case of the 10 mg/kg dose and concomitant saturation of elimination kinetics at the higher dose (20 mg/kg). The apparent elimination t1/2 of FL markedly increased and the metabolite-to-parent drug ratio declined with the higher dose, this also being consistent with saturable elimination.(ABSTRACT TRUNCATED AT 250 WORDS)
Parlodel SRO, a new slow release form of bromocriptine, was studied in 26 patients with tumoral and non-tumoral hyperprolactinemia. Prior to the treatment, serum prolactin (PRL) levels ranged from 45 ng/ml to 7000 ng/ml and they decreased to within the normal range in all but one patient after 7 days-1 year of treatment with this new formulation of bromocriptine. The clinical improvement paralleled the normalization of PRL secretion. Tolerability was rated good or very good in 24 patients, even in the three patients who had been intolerant of oral Parlodel. In conclusion, Parlodel SRO administered as a single daily dose resulted in very effective lowering of serum PRL in patients with hyperprolactinemic disorders.
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