抄録
The ICH Guideline S6R1 (draft) recommends that the potential for effects on reproductive functions can be assessed in repeat dose ( 3 months) toxicity studies when non-human primate is the only relevant test species. Male reproductive parameters routinely evaluated include testicular volume, semen analyses, reproductive hormone levels, and testicular histopathology. Background reference data of cynomolgus monkey is provided in this presentation as a guide. Testicular volume (TV), semen analysis including sperm motility (SM), sperm concentration (SC) and total sperm count per ejaculation (TSC), and serum testosterone (TE), inhibib-B (IB) and lutenizing hormone (LH) concentrations were measured or analyzed twice during pre-dose period, and 1st＜, 2nd and 3rd months of the dosing period. The differences between the 1st and 2nd pre-dose time-points were 8% in TV, 18% in SM, 117% in SC, 108% in TSC, 46% in TE, 57% in IB and 16% in LH. The mean pre-dose values (baseline) were 38.2 mL in TV, 77% in SM, 949.4 x106/mL in SC, 184.9 x106/ejaculation in TSC, 6.4 ng/mL in TE, 513.2 pg/mL in IB, and 0.38 ng/mL in LH. Mean value at each dosing timepoint varied from the baseline for 9-15% in TV, 12-15% in SM, 47-91% in SC, 48-92% in TSC, 62-92% in TE, 33- 62% in IB, and 15-29% in LH. Based on these data, testicular volume, sperm motility and LH show greater accuracy in reproducibility. Sperm concentration, total sperm count per ejaculation, and testosterone and inhibin-B concentrations vary between samples. Multiple time-points are required to establish each animal’s baseline data.
