Several peptide hormones are effective when administered intranasally (in); these include oxytocin, vasopressin, insulin, glucagon, and calcitonin. With regard to GHRH and CRH, previous studies demonstrated that their bioavailability following in administration was very low. In this study we evaluated the serum GH response to 50 micrograms GHRH iv and to 700 micrograms GHRH in, the latter given alone and with 5 and 15 mg sodium-glycocholate (SGC), a surfactant, in six normal men. The bioavailability of in GHRH, calculated as net GH secretory area, was very low, and increased to 7% that of iv GHRH when SGC was used. In the same men, 50 micrograms CRH was administered both iv and in, alone and with 5 and 15 mg SGC. The bioavailability of in CRH, calculated as net cortisol secretory area, was very low and increased to 100% that of iv CRH when 15 mg SGC was used. These data indicate that the efficacy of GHRH and CRH administered in is significantly augmented by SGC.

The pharmacokinetics of intranasal, an intravenous infusion, and intramuscular glucagon has been studied in 5 healthy subjects and 11 patients with insulin-dependent diabetes mellitus. After infusion the elimination half-life was significantly longer in diabetics (11.9 vs 6.6 min) and the apparent volume of distribution was twice as high in diabetics (0.19 vs 0.37 l.kg-1). The metabolic clearance rates were the same in the two groups (18.9 and 21.3 ml.min-1.kg-1 in controls and in diabetics) and were about twice those previously reported. After 1 mg intranasally the Cmax of immunoreactive glucagon (IRG) was similar in diabetic and in healthy subjects. Administration of a higher dose (2 mg) to diabetic patients produced a higher plasma level, although not proportionately so. The AUC after 1 mg was also similar in controls and in diabetics. The elimination half-life in both groups was similar to the value found after i.v. infusion; it was significantly shorter in controls (5.5 min) than in diabetics (13.8 min). In both groups, mean Cmax was significantly lower than after IM glucagon, the relative bioavailability of 1 mg intranasally vs IM injection being less than 30%. After IM administration, the Cmax and AUC of IRG in controls and in diabetic patients, were identical. The apparent elimination half-life was also similar in the two groups, and was three- to four-times longer (28.6 and 31.4 min) than after infusion or intranasal administration, possibly because estimation of the t1/2 was affected by slow release of the hormone from the site of injection.

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Combined testing of the pituitary gland by administration of GHRH, CRH, GnRH and TRH has been proposed for clinical studies, although some reports indicate that individual endocrine responses can be different when releasing hormones are used alone or in combination. Aims of this study were to evaluate: 1) the reproducibility of the combined test on different days; 2) the endocrine responses to the combined test applied twice at 3h and at 5h interval; 3) differences of endocrine responses in young and in elderly men. Six healthy young men (aged 25 to 35 yr) and 6 healthy elderly men (aged 65 to 75 yr) were evaluated: elderly men had lower testosterone, free T3, and somatomedin-c levels than young men, while 17 beta-estradiol and inhibin were not significantly different, all values being within normal laboratory limits. The 12 men were tested on day 1 with iv GHRH (50 micrograms) CRH (50 micrograms), GnRH (100 micrograms) and TRH (200 micrograms) at 08:00h and again at 11:00h; on day 8, the same men were tested at 08:00h and again at 13:00h. At 08:00h, the endocrine responses were similar on day 1 and on day 8. The second GH (young and elderly men) and PRL (only young men) response was blunted on day 1, when the interval between two consecutive stimuli was 3h, but not on day 8, when the interval was 5h. Elderly men differed from young men only for GH and for PRL release on day 1 at 08:00h.(ABSTRACT TRUNCATED AT 250 WORDS)

The attempt has been made to identity the lowest dose of glipizide, a second generation sulphonylurea, capable of improving glucose tolerance in overweight and obese subjects with various degrees of glucose tolerance. Thirty one obese subjects, 12 with non insulin dependent diabetes mellitus (NIDDM), 9 with impaired glucose tolerance (IGT) and 10 with normal glucose tolerance (NGT) each underwent four OGTTS (75 g), at 1 week intervals, after administration in random order of placebo or glipizide 0.5, 1.0 or 2.5 mg 30 min before glucose. Glucose tolerance in all groups was progressively improved by the increasing doses of glipizide and was normalized by 1.0 mg glipizide in impaired glucose tolerance (IGT) and by 2.5 mg glipizide in NIDDM. Insulin release was not significantly affected by glipizide in the three groups of subjects. The data indicate that it is possible, at least in acute experiments, to improve glucose tolerance in overweight and obese subjects with IGT, with NGT and with NIDDM, with doses of glipizide that do not affect insulin release.