Acute and long-term effects of once-daily oral bromocriptine and a new long-acting non-ergot dopamine agonist, quinagolide, in the treatment of hyperprolactinemia: a double-blind study.

Quinagolide (CV 205-502, Sandoz), an octahydrobenzo (g) quinoline, is a new non-ergot dopamine agonist which has specific D2 receptor activity and a long half-life, making it suitable for once-daily treatment. Recent uncontrolled reports have suggested that quinagolide may be successfully used for the clinical management of hyperprolactinemia with fewer adverse reactions than bromocriptine. This study is the first to compare quinagolide in a double-blind manner with bromocriptine, given only once-daily instead of the usual multidose regimen. In the first phase we compared, in 7 hyperprolactinemic patients, the effects over 24 h of a single oral dose of 0.05 mg quinagolide with 2.5 mg bromocriptine. Compared with placebo, both bromocriptine and quinagolide showed potent PRL-inhibiting and GH-releasing effects, with comparable effects at 24 h; no significant changes were observed in TSH, LH, FSH or cortisol. Twelve hyperprolactinemic patients were then randomized to receive either once-daily bromocriptine or quinagolide in incremental doses for a period of six months. Both drugs were found to be equally effective, and no differences were seen either in adverse reactions or PRL levels during repeated diurnal sampling. We therefore conclude that quinagolide and bromocriptine are therapeutically equivalent in long-term use, and both are equally effective when given once a day. However, some patients intolerant of bromocriptine may respond better to quinagolide, and vice versa.

Pyridostigmine fails to increase either spontaneous or GHRH-stimulated GH secretion during day or night in growth hormone-insufficient children.

OBJECTIVE The aim of the study was to investigate whether pyridostigmine, a cholinesterase inhibitor which is thought to act at the hypothalamus to inhibit somatostatin secretion, would augment spontaneous or GHRH-stimulated serum GH levels in patients with GH-insufficiency. DESIGN Oral pyridostigmine 60 mg or placebo was administered at the start of a 9-h subcutaneous infusion of either GHRH (1-29)NH2 10 micrograms/kg/h or saline control. Studies were performed during the daytime (0900-1800 h) in five patients, and the night-time (2100-0600 h) in a further five. PATIENTS Ten short, pre-pubertal children (aged 6-11 years; eight boys) with growth hormone insufficiency were studied. MEASURES Blood for serum GH was sampled every 20 min, and analysed using the PULSAR program. RESULTS The subcutaneous infusion of GHRH 10 micrograms/kg/h increased mean serum GH levels (+/- SEM): by day 17.7(+/- 6.8) vs placebo 2.2(+/- 0.4) mU/l (P less than 0.01), and by night 26.9(+/- 3.3) vs 5.5(+/- 1.3) mU/l (P less than 0.05). There was a significant rise in mean 'baseline' GH concentration: by day 5.5(+/- 1.7) vs 1.0(+/- 0.0) mU/l (P less than 0.05); and night 8.2(+/- 2.7) vs 1.3(+/- 0.3) mU/l (P less than 0.05). Pyridostigmine failed to produce a significant overall increase in either spontaneous or GHRH-stimulated GH secretion by day or night, although there was a significant rise in mean GH levels during the 3 h following pyridostigmine administration in the morning: 4.4(+/- 1.1) vs 2.4(+/- 0.5) mU/l (P less than 0.001). GHRH or pyridostigmine given singly or in combination had no significant effect on the number of pulses. Side-effects attributable to pyridostigmine occurred in seven children. CONCLUSIONS Pyridostigmine, either on its own or as an adjuvant therapy in combination with GHRH, acts for only a brief time and does not offer any potential benefit in the management of children with short stature.