Reversible plasma and red blood cells volumes increases in acromegaly.

Plasma volume (PV) and red blood cells volume (RBCV) were measured in 76 normotensive acromegalic patients (42 males and 34 females) and compared with those of 28 controls on the basis of body surface. In untreated males PV and RBCV were significantly higher than in normals (P less than 0.001) and total blood volume (TBV) was above the normal range in 85%. Untreated females also showed an elevated PV but had significantly lower RBCV than the male patients. The only vascular volume of the patients with correlated significantly with the body weight or surface was RBCV in females. One to five studies were done after treatment in 52 patients and analyzed as a function of plasma GH levels. Plasma volume reverted to the normal range (males) or was significantly lower than in untreated patients (females) in the groups of patients with normal GH levels while RBCV normalized at higher GH concentrations. At similar GH levels, treated patients without pituitary failure (n = 35) or given T4 and/or cortisol substitution for hypopituitarism showed similar vascular volumes. The plasma volume and TBV in both sexes and RBCV in males was significantly correlated with Log 10 GH levels. It is concluded from these data and other experimental evidence that endogenous GH hypersecretion is responsible for the reversible PV and RBCV increases frequently found in acromegalic patients.

Single and repeated dose kinetics of the hypnotic agent loprazolam in healthy volunteers.

The pharmacokinetics of loprazolam have been studied in eight healthy male volunteers after single and repeated 2 mg oral doses taken at night, for eight nights. The absorption and disposition of unchanged drug (HPLC-GC assay) and receptor active benzodiazepine-type materials (radioreceptor assay) were examined after the first and eighth dose. Maximum levels of approximately 10 ng ml-1 (range 3.6 to 15.5 ng ml-1) were reached within about 2.5 h after dosing. The post-peak levels declined in a single exponential fashion with an overall mean +/- SD half-life of 7.06 +/- 1.98 h and total areas under the curve ranging from 35.9 to 189.0 ng ml-1 h. There were no statistical differences between the values for the first and eighth doses. There was no evidence to suggest that significant accumulation of parent drug or receptor active benzodiazepine-type materials had occurred, and it is concluded that the kinetics of loprazolam would allow repeated daily doses of 2 mg.