Pharmacokinetics of non-steroidal anti-inflammatory drugs in male rabbits after acute and chronic administration and effect of chronic treatment on seminal prostaglandins, sperm quality and fertility.
The pharmacokinetics of various non-steroidal anti-inflammatory drugs were determined to find dosage regimens by which drug concentrations known as active from human anti-inflammatory therapy could be reached and maintained in rabbits during continued administration. Based on the pharmacokinetics and side-effects of the different drugs, phenylbutazone was selected for the fertility experiments. Treatment of male rabbits with phenylbutazone for 9 consecutive days significantly reduced seminal concentrations of PGE-2 and PGF-2 alpha and tended to increase ejaculate volumes, sperm motility, and fertility. These results indicate that, at least in rabbits, inhibition of PG synthesis by prolonged treatment with non-steroidal anti-inflammatory drugs does not impair male fertility. Instead, chronic treatment with the drugs at non-toxic doses may improve sperm quality and fertility.
Löscher
W
W
Laboratory of Pharmacology and Toxicology, School of Veterinary Medicine, Free University of Berlin, Federal Republic of Germany.
Lüttgenau
H
H
Schlegel
W
W
Krüger
S
S
D000818:Animals; D015237:Dinoprost; D015232:Dinoprostone; D004334:Drug Administration Schedule; D005298:Fertility / Q000187:drug effects*; D008297:Male; D010653:Phenylbutazone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011453:Prostaglandins / Q000378:metabolism*; D011458:Prostaglandins E / Q000378:metabolism; D011460:Prostaglandins F / Q000378:metabolism; D011817:Rabbits; D012661:Semen / Q000378:metabolism*; D013094:Spermatozoa / Q000187:drug effects*
D011453:Prostaglandins; D011458:Prostaglandins E; D011460:Prostaglandins F; D015237:Dinoprost; D010653:Phenylbutazone; D015232:Dinoprostone