Metabolic Clearance of Human Chorionic Gonadotrophin Administered to Non Pregnant Women

Abstract

A large single dose (94 000 to 131 000 IU) of human chorionic gonadotrophin (HCG) was administered intravenously to three amenorrhoeic women and the plasma levels and urinary elimination of HCG were followed by a bioassay method and a radioimmunoassay procedure in parallel. There was a close agreement between the estimates of HCG obtained by the two methods in the urine, but not in the plasma, where bioassays gave significantly (P < 0.001) higher estimates of potency than immunoassays. The disappearance rate of the injected HCG from the plasma was calculated on the assumption that the logarithm of the plasma concentration of HCG is linearly related to the time elapsed following its administration. There was a satisfactory parallelism between the regression lines obtained by the two methods. The half-life time of administered HCG in circulating plasma varied between 6 and 10 hours, with a mean value of 8 hours. From the relationship of the initial plasma concentration and dose administered, the plasma distribution volume of the hormone was tentatively calculated. The calculated plasma volumes (1664 ml from bioassays and 3680 ml from immunoassays) suggested that the bioassays gave most probably an overestimate and the immunoassays an underestimate of the HCG present in the plasma. On the basis of different assumptions it was calculated that the metabolic clearance rate of HCG was around 4 ml/min. The urinary excretion of the administered HCG by the three subjects amounted to 21 to 22 per cent of the injected material, estimated both by the bioassay and immunoassay methods. The renal clearance of the injected hormone was 0.36 ml/min when calculated from the bioassay data and 0.70 ml/min on the basis of immunoassays. Since the half-life time of circulating HCG is considerably longer than that reported for human luteinising hormone of pituitary origin, it should be realized that repeated daily injections of HCG will result in a progressive accumulation of the hormone in the circulation.

hCGbeta core fragment is a metabolite of hCG: evidence from infusion of recombinant hCG

“…The percentage of injected hCG excreted in the urine, as the dimer, has been reported to vary from 17% to 28% (Wide et al 1968, Wehmann & Nisula 1981. We also found a variable fraction of r-hCG excreted (10·1-17·3%), with a lower mean percentage.…”

“…The renal clearance rate determined by Wide et al (1968) was 0·77 ml/min in the first 6 h and 0·64 ml/min in the 7-24 h period, when an immunoassay was used, and 0·39 ml/min and 0·34 ml/min, for the same respective periods, when calculated from bioassay results. Wehmann & Nisula (1981), using highly purified urinary hCG, reported the renal clearance rate to be 0·7 ml/min.…”

“…Previous studies on the pharmacokinetics and metabolism of hCG have indicated a multi-exponential disappearance curve in serum (Midgely & Jaffe 1968, Yen et al 1968, Rizkallah et al 1969, Wehmann & Nisula 1981, Korhonen et al 1997 and that only 17-28% of the serum hCG is excreted in the urine as the intact heterodimeric form (Wide et al 1968, Wehmann & Nisula 1981. In addition to a wide range of heterogeneous forms of intact hCG, the urine of pregnant females contains free and free subunits, nicked hCG (missing linkages in the 41-54 region) (Puisieux et al 1990 and C-terminal forms, i.e.…”

Metabolic and renal clearance rates of purified human chorionic gonadotropin.

“…The metabolism of human chorionic gonadotropin (hCG)1 has been the subject of a number of reports during the past 40 yr (1)(2)(3)(4)(5)(6)(7)(8)(9)(10). It has been established that the hCG molecule has a plasma metabolic clearance rate (MCR) that is quite slow relative to the MCR of the pituitary glycoprotein hormones (1)(2)(3)(4)(5), and that urinary excretion accounts for some, but not all, of the metabolic disposal of hCG (1,2,(5)(6)(7)(8)(9)(10).…”

“…It has been established that the hCG molecule has a plasma metabolic clearance rate (MCR) that is quite slow relative to the MCR of the pituitary glycoprotein hormones (1)(2)(3)(4)(5), and that urinary excretion accounts for some, but not all, of the metabolic disposal of hCG (1,2,(5)(6)(7)(8)(9)(10). Techniques for quantitation of hCG metabolism have varied, and each has its limitations.…”