Abstract. The disappearance rate of [D-Ser(t-bu)6,des-Gly10]GnRH ethylamide (Buserelin®, HOE 766) was studied in plasma and urine after intranasal (300 μg) or sc (10 μg/kg) administration. A radioimmunoassay for HOE 766 was developed using 125I[D-Trp6,Des-Gly10]GnRH ethylamide as tracer and an antiserum raised against HOE 766. Cross-reaction with native GnRH was only 1.7%. Sensitivity was 1 pg/tube. In 6 male adolescents, the mean plasma HOE 766 concentration (± sem) was 0.46 ± 0.08, 0.50 ± 0.10, 0.28 ± 0.04, 0.24 ± 0.04, 0.13 ± 0.03, and 0.08 ± 0.02 μg/l 30, 60, 90, 120 and 180 min after the intranasal administration, respectively. Concomitant urinary excretion of HOE 766-like material was 9.43 ± 1.96 μg/4 h. There was a good correlation between integrated plasma levels and urinary excretion (r = 0.92). In the same 6 volunteers, the plasma HOE 766 levels were 21.2 ± 3.0, 25.9 ± 0.8, 21.2 ± 0.9, 17.1 ± 0.7, 12.8 ± 1.1, 8.9 ± 0.4, and 5.9 ± 0.8 μg/l 20, 40, 60, 90, 120, 180 and 240 min after sc injection, respectively. The mean urinary excretion was 543 ± 61 μg/4 h. In two girls with precocious puberty treated during 12 to 15 months with intranasal administration of HOE 766, urinary excretion of HOE 766-like material was shown to correlate well with the degree of inhibition of plasma 17β-E2and of plasma LH and FSH responses to a GnRH challenge. Thus, monitoring of HOE 766 in urine appears to be helpful for evaluating of intranasal therapy with a GnRH analog in precocious puberty.
Establishing intranasal administration as an alternative to intravitreal delivery of fluorescent annexin
