Absence of reproductive and developmental toxicity in rats following oral dosing with nelfinavir.
The potential for nelfinavir mesylate (VIRACEPT) to produce reproductive toxicity was evaluated in rats administered oral doses of 200, 500, or 1000mg/kg/day. In the fertility and early embryonic development to implantation study, male rats were treated beginning 28 days prior to mating until necropsy and females for 2 weeks prior to mating and through gestation day (GD) 7. In the pre- and postnatal development study, pregnant rats were treated from GD 6 through lactation day (LD) 20. Selected F(1) pups from this study were evaluated in sensory and behavioral tests and were subsequently mated. Pregnant F(1) females were euthanized on GD 20 and their F(2) fetuses were examined. F(1) animals were not directly dosed with the drug. No treatment-related effects were observed on any male reproductive parameters. Administration of nelfinavir did not produce adverse effects on fertility, pregnancy, embryo-fetal development, parturition, or lactation in the F(0) generation. Similarly, no adverse effects of nelfinavir treatment were observed on pre- and postnatal growth, development, reproductive performance and embryo-fetal development in the F(1) offspring. Based on the results of this study, the no-observed-adverse-effect-level (NOAEL) for developmental and reproductive toxicity in rats was considered to be 1000mg/kg/day, the highest dose tested.
Burns-Naas
Leigh Ann
LA
Worldwide Safety Sciences, Pfizer Global Research and Development, 10724 Science Center Drive, San Diego, CA 92064, USA. leighann.burns@pfizer.com
Stump
Donald G
DG
Webber
Stephanie
S
Holson
Joseph F
JF
Masarjian
Lilit
L
Furman
Grace
G
Zorbas
Mark
M
D000284:Administration, Oral; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000502:physiology; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005314:Embryonic and Fetal Development / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005298:Fertility / Q000187:drug effects / Q000502:physiology; D005333:Fetus / Q000187:drug effects; D007774:Lactation / Q000187:drug effects; D008297:Male; D008431:Maternal-Fetal Exchange; D008844:Micrognathism; D019888:Nelfinavir / Q000008:administration & dosage* / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors; D014059:Tongue / Q000002:abnormalities
D019888:Nelfinavir