178 D-SER(TBU)6EA9lHRH IN PRECOCIOUS PUBERTY: PHARMACO-KINEIICS OF SC IV AND INTRANASAL USE

The LHRH analog,D-Ser(TBU)6EA9LHRH(LHRHa) effectively controls the clinical and endocrinological progress of central precocious puberty in both sexes, when provided once daily by SC injection, or by intra-nasal (IN) spray given 8 hourly (J. Clin.End. & Metab.1984: 58,966). To define the pharmacokinetics of LHRHa in this condition, we developed a RIA,utilizing an antibody generated against a hemocyanin conjugate of LHRHa, in which there is no crossreactivity with natural LHRH, LH or FSH. Recovery by RIA of added LHRHa in normal human serum or urine, ranged from 93 to 105%. During treatment with SC injection,30 μg/kg, peak levels of LHRHa of 42.1 ± 7.4 ng/ml (mean ± SEM) occurred at 30 min, with t½ of 71.4 min (n,5). Only 21% of given dose was excreted in urine at +3 h. With the IN route, 5.3 μg/kg (200 μg fixed dose) peak levels were seen at 30 min (n,7) but were 1000 fold lower in concentration (0.34 ± 0.13 ng/ml). Only 0.6% of the dose was excreted at +3 h. After IV injected 10 μg/kg in 3 adult volunteers, peak levels of >3500 ng/ml occurred at 1-2 min, t½β was 38.2 min and 17.4% was recovered in urine at 3 h. These data indicate:(1) t½ and elimination rate of this LHRHa is significantly greater than natural LHRH; (2) low dose LHRH at frequent intervals probably provides optimal treatment; (3) urinary LHRHa by specific RIA can be used as a guide to patient compliance.