PHARMACOKINETICS AND PHARMACODYNAMICS OF A SINGLE-DOSE OF RECOMBINANTHUMAN GROWTH-HORMONE AFTER SUBCUTANEOUS ADMINISTRATION BY JET-INJECTION - COMPARISON WITH CONVENTIONAL NEEDLE-INJECTION

The pharmacokinetics and pharmacodynamics of recombinant human growth hormone (rhGH) were studied after a single subcutaneous dose given by jet-injection, and have been compared with the results obtained after conventional needle-injection. Twelve healthy male volunteers complete d an open label, randomised, two-way crossover study, with a 7-day was hout period between the two single sc doses. Pharmacokinetic parameter s were derived from rhGH concentrations in blood samples collected reg ularly over 24 h after dosing on Day 1 of each period. To investigate the pharmacodynamics, additional samples were taken for the analysis o f somatomedin C (IGF-I) and free fatty acids (FFA). A higher and earli er C-max was found after jet-injection (ratio (%) jet-injected/needle- injected 124; 90%-confidence interval 108 - 142). The AUC(0-infinity) for rhGH were similar (ratio (%) jet-injected/needle-injected 98; 90%- confidence interval 93 - 103). Both treatments were associated with a significant and similar rise in IGF-I. Both administrations of rhGH we re associated with identical rhythmical changes in FFA. The study indi cates that jet-injected and needle-injected rhGH are bioequivalent wit h respect to the amount absorbed. The criterion for bioequivalence is not met for the rate of absorption. It is unlikely that the latter fin ding will influence the pharmacodynamics of rhGH, since bioequipotency was established for the effect on IGF-I generation. Jet-injection was safe in use and was generally well tolerated.