Pharmacokinetics of biosynthetic and pituitary human growth hormones in rats

The pharmacokinetics of biosynthetic and pituitary human growth hormones (B-hGH and P-hGH) was compared in rats. Normal and hypophysectomized male and female rats were subcutaneously and intramuscularly injected with 100 micrograms/kg B-hGH and P-hGH and intravenously with 60 micrograms/kg B-hGH and P-hGH. A statistically significantly smaller distribution volume and a slower metabolic clearance rate (MCR) was found for B-hGH compared to P-hGH. A statistically significantly smaller distribution volume and MCR was found for hypophysectomized rats compared to normal rats. The plasma half lives were estimated to be about 3-7 min. (alpha 1/2) and 29 min. (beta 1/2). The plasma levels of hGH were higher after subcutaneous compared to intramuscular administration. The data imply that an extensive local degradation took place at the subcutaneous and intramuscular injection sites. Comparative tissue distribution studies were performed with radioiodinated B-hGH and P-hGH. No differences were observed between the growth hormones. It was found that most of the labelled TCA precipitable material was cleared through the liver. The females cleared relatively more through the liver than the males, while the males cleared relatively more through the kidneys.