U. JODAL6, L. REES8, S.P.A. RIGDEN8 and M.A. PREECE9 From 2the Hbpital Universitaire des Enfats Reine Fabiola, Brussels. 3Vniversitair Ziekenhuis Gasthuisberg, Leuven, 4Childrenf Hospital, Universiry of Helsinki, Helsinki, sHbpital des Enfats Malades. Paris, %tra sjukhuset, Gothenburg. 7Huddinge sjukhus. Stockholm, 8Guy's Hospital. London, %e Hospital for Sick Children, London and I Kabi Pepride Hormones, Stockholm. M. VANDERSCHUEREN-LODEWEYCKX3, C. HOLMBERG4, I. SIPILA4, ABSTRACT. Johansson, G.I. Sietnieks, A.I. Janssens, F.2, Proesmans, W.3, Vanderschueren-lodeweyckx, M.3, Holmberg, C.4, Sipila, L4, Broyer, M.5, Rappaport, R.5, Albertsson-Wikland, K.6, Berg, U7, Jodal, L6, Rees, L.8, Rigden, S.P.A.8 and Preece, M.A.9 (2Hi5pital Universitaire des Enfants Reine Fabiola, Brussels, 3Universitair Ziekenhuis Casthuisberg, Leuven, 4Children's Hospital, University of Helsinki, Helsinki, 5HOpital des Enfants Malades, Paris, G t r a sjukhuset, Gothenburg, 7Huddinge sjukhus, Stockholm, 8Cuy's Hospital, London, q h e Hospital for Sick Children, London, and IKabi Peptide Hormones, Stockholm). Recombinant human growth hormone treatment in short children with chronic renal disease, before transplantation or with functioning renal transplants: an interim report on five European studies. Acta Paediatr Scand [Suppl] 370: 36-42, 1990.Growth retardation is common in children with chronic renal disease. Final adult height is often reduced, even in children with a functioning renal transplant. The five European studies considered here aim to investigate the efficacy and safety of recombinant human growth hormone therapy (rhGH) in two groups of short children with chronic renal disease. The first group comprises 29 prepubertal children with preterrninal chronic renal failure (i.e. before renal transplantation), and the second group comprises 39 prepubertal and pubertal children with functioning renal transplants. The median bone age retardation in the groups at the start of treatment was between 2.2 and 3.7 years; this did not change during the first year of treatment. This interim report concentrates on patients who have been treated for at least 1 year (i.e. 22 children from the first group, and 28 children from the transplant group (15 prepubertal and 13 pubertal children). The median height velocity increased from 4.8 cmlyear to 10.0 cmlyear in the first group (the chronic renal failure group), from 2.6 cmlyear to 6.2 cmlyear in prepubertal children with renal transplants and from 3.8 cmlyear to 6.7 cmlyear in pubertal children with renal transplants. The corresponding changes in height velocity SDS were from -1.3 to 5.1 for the chronic renal failure group and -2.8 to 2.3 for the prepubertal children with renal transplants. Renal function declined in the chronic renal failure group but this decline corresponded to expected progression of the disease. Some o f the children with renal transplants showed a decreased renal. function, which in most cases was explained by non-compliance or chronic rejection.Growth retardation is common...

The pharmacokinetics of recombinant human insulin-like growth factor I (rhIGF-I) were studied in healthy volunteers and in patients with growth hormone receptor deficiency (GHRD; Laron syndrome). Following single subcutaneous injections of rhIGF-I, 40 and 80 micrograms/kg, to healthy volunteers, the peptide was absorbed slowly, with a maximum concentration reached after about 7 hours. Following daily multiple subcutaneous injections of rhIGF-I, 40 micrograms/kg, trough concentrations of IGF-I were increased by 277 +/- 50 micrograms/l (mean +/- SD) from baseline. IGF-I was thus characterized as a low-clearance peptide, with a clearance and half-life estimated at about 0.20 ml/minute/kg and 20 hours, respectively, in healthy volunteers. The volume of distribution was low, about 0.20-0.36 litres/kg, the bioavailability of subcutaneously administered rhIGF-I was 100%, and the rate of production of IGF-I was estimated to be about 50 micrograms/kg/day (3.5 mg/day). Patients with GHRD had low baseline IGF-I concentrations (30-50 micrograms/l) and a much more rapid turnover of IGF-I compared with that in healthy volunteers. The clearance and half-life of IGF-I were estimated to be about 0.60 ml/minute/kg and 6 hours, respectively. The volume of distribution was about the same as in healthy subjects. Due to the rapid turnover of IGF-I, trough IGF-I concentrations were increased to just above baseline during subcutaneous injections of 40 micrograms/kg once daily for 7 days. The maximum increase in IGF-I levels was 111 +/- 12 micrograms/l and 150 +/- 3 micrograms/l following daily subcutaneous injections of 40 x 1 and 40 x 2 micrograms/kg for 7 days, respectively.

No abstract

The pharmacokinetic profile of recombinant human insulin‐like growth factor I (IGF‐I) was studied in healthy volunteers. Following a single subcutaneous injection of 40 μg/kg or 80 µg/kg,mean serum IGF‐I concentrations increased by 150 ng/ml and 245 ng/ml, respectively. During repeated daily injections of 40 μg/kg, a steady‐state IGF‐I level of 150 ng/ml above baseline was reached. Of the pharmacokinetic indices measured, only Tmax, varied between single and multiple dose regimens (6.9 hours versus 3.5 hours). No hypoglycaemic symptoms were observed, and after injection of IGF‐I no depression of endogenous IGF‐I production was observed. Fasting insulin levels were unaltered, but insulin was lowered by IGF‐I with respect to placebo.

Copulatory behavior in the ovariectomized rat, the lordotic response (L.R.), was induced by estrogen followed by progesterone. L.R. is inhibited by lysergic acid diethylamide (LSD) (greater than or equal to 0.05 mg/kg) and by Levo-5-hydroxytryptophan (L-5-HTP) (greater than or equal to 2.5 mg/kg). The effects of the putative 5-HT antagonists lisuride, metergoline, methysergide, mianserin, cinanserin, cyproheptadine, pirenperone and altanserin on the LSD-induced inhibition of L.R. were tested. Lisuride, metergoline, methysergide and mianserin were found to have no LSD-blocking effect. In contrast, cinanserin, cyproheptadine and pirenperone acted antagonistically to LSD, within a critical dose range. The selective 5-hydroxytryptamine2 (5-HT2) receptor antagonist altanserin effectively prevented the LSD-induced inhibition of L.R., and the doses required (0.05-0.20 mg/kg) indicated a comparatively high antagonistic potency. In addition altanserin (0.2 mg/kg) effectively prevented the lordosis inhibitory effect induced by L-5-HTP (2.5 mg/kg), after pretreatment with pargyline and RO4-4602. It is suggested that the suppression of copulatory behavior caused by LSD and L-5-HTP is mediated by 5-HT2 receptors.