The effects of oral sumatriptan, a 5-HT1 receptor agonist, on circulating ACTH and cortisol concentrations in man.

1. The effects of oral sumatriptan (50, 100 and 200 mg), a 5-HT1 receptor agonist, and placebo, on circulating adrenocorticotrophic hormone (ACTH) and cortisol concentrations were determined over 24 h after dosing, in 26 healthy male subjects. ACTH was measured by immunoradiometric assay and cortisol by radioimmunoassay. 2. After sumatriptan all subjects displayed a normal diurnal rhythm for circulating ACTH and cortisol compared with placebo. 3. There was a reduction in the trough circulating ACTH concentration over 0-4 h which was 18% with 100 mg (P = 0.002), and 25% with 200 mg (P < 0.001). The 5 h, post-prandial, peak ACTH concentration was reduced by 21% with 100 mg (P = 0.018) and by 20% with 200 mg (P = 0.024). The weighted mean ACTH over 24 h was reduced by 8% with 100 mg (P = 0.029) and by 8% with 200 mg (P = 0.018). The nadir concentration of ACTH over the 24 h and the ACTH concentration 24 h after sumatriptan were not, however, significantly reduced. All results are compared with placebo. 4. There was a reduction in the trough circulating cortisol concentration over 0-4 h which was 15% with 50 mg (P = 0.015), 14% with 100 mg (P = 0.022) and 24% with 200 mg (P < 0.001). The 5 h, post-prandial, peak cortisol concentration was reduced by 16% with 100 mg (P = 0.012) and by 15% with 200 mg (P = 0.017).(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative pharmacokinetics of temazepam Gelthix and liquid-filled soft gelatin capsules.

An open, randomized, cross-over study involving 24 healthy volunteers, shows that a novel formulation of temazepam (temazepam Gelthix, TG) in soft gelatin capsules designed to resist i.v. abuse has a similar pharmacokinetic (P-K) profile to that of a liquid-filled, reference formulation (TL) when administered as a single oral dose of 20 mg. The relative bioavailability of the two formulations assessed in terms of the area under the time versus plasma concentration profile (AUC), although statistically different (P less than 0.05), is well within the acceptable 80-120% limits for bioequivalence. Although the mean Cmax for TG (616.6 ng/ml) is lower than for TL (707.9 ng/ml) and the median time to reach Cmax (Tmax) is 40 min (TG) vs. 30 min (TL), there is no significant difference between TG and TL either in their absorption constant (Ka) (0.123 vs. 0.138 min-1 respectively) or their distribution (a) (29.5 vs. 32.4 min) and elimination (beta) (6.3 vs. 6.6 h) half-lives (t1/2). Thus the essential P-K characteristics for the use of temazepam as a hypnotic and premedicant, specifically a rapid rise followed by a prompt fall in blood levels, are conserved by the Gelthix formulation.

Amino acid imbalance in cystinuria.

After oral ingestion of a free amino acid mixture by three cystinuric patients, plasma increments of lysine and arginine were lower and those of many other amino acids were significantly higher than those found in control subjects. Similar results were obtained in control subjects after amino acid imbalance had been artificially induced by the omission of cystine, lysine, and arginine from the amino acid mixture. Especially high increments of alanine and proline provided the best evidence of amino acid imbalance caused by a temporary lysine and, to a lesser extent, arginine and cystine deficit. No such amino acid imbalance was found to occur in the cystinuric patients after ingestion of whole protein, indicating that absorption of oligopeptides produced by protein digestion provided a balanced physiological serum amino acid increment. This is considered to explain the lack of any unequivocal nutritional deficit in cystinuric patients despite poor absorption of the essential free amino acid, lysine.