Comparative pharmacokinetics and pharmacodynamics of a PEGylated recombinant human growth hormone and daily recombinant human growth hormone in growth hormone-deficient children

OBJECTIVE: Recombinant human growth hormone (rhGH) replacement therapy in children generally requires daily subcutaneous (sc) injections, which may be inconvenient for patients. Jintrolong(®) is a PEGylated rhGH with the purpose of weekly sc injections. The aim of the current study was to examine the pharmacokinetics, pharmacodynamics, safety, and tolerability of multiple sc doses of Jintrolong(®) vs daily doses of rhGH. DESIGN AND METHODS: Twelve children with growth hormone deficiency participated in this single-center, open-label, crossover Phase I trial. All subjects received daily sc injections of rhGH at 0.0286 mg/kg/d for 7 days, followed by a 4-week washout period and six weekly doses of Jintrolong(®) at 0.2 mg/kg/w. RESULTS: In comparison with rhGH, sc injection of Jintrolong(®) produced a noticeably higher C(max), significantly longer half-life (t(1/2)), and slower plasma clearance, signifying a profile suitable for long-term treatment. The ratio of the area under the concentration vs time curve (AUC) after the seventh and first injections (AUC((0–∞)7th)/AUC((0–∞)1st)) of rhGH was 1.02, while the AUC((0–∞)6th)/AUC((0–∞)1st) of Jintrolong (®) was 1.03, indicating no accumulation of circulating growth hormone. There was no significant difference in the change in insulin-like growth factor-1 expression produced by 7 days of sc rhGH and weekly Jintrolong(®) injections. There were no severe adverse events during the trial. CONCLUSION: The elimination rate of Jintrolong(®) was slower than that of sc rhGH. No progressive serum accumulation of Jintrolong(®) was found. The changes in insulin-like growth factor-1 expression produced by rhGH and Jintrolong(®) were comparable, indicating similar pharmacodynamics. Our results demonstrate that Jintrolong(®) is suitable for long-term growth hormone treatment in children with growth hormone deficiency.