Highly water-soluble prodrugs of anthelmintic benzimidazole carbamates: synthesis, pharmacodynamics, and pharmacokinetics.
Highly water-soluble prodrugs 1a- g of anthelmintic benzimidazole carbamates 2a- g were synthesized. These prodrugs combine high aqueous solubility and stability with high lability in the presence of alkaline phosphatases. The veterinary utility of 1a was shown by a pharmacodynamic and pharmacokinetic study performed in swine. Comparable anthelmintic efficacy was observed with prodrug 1a or the parent fenbendazole 2a. The pharmacokinetic results showed that 2a is better absorbed when derived from 1a than when applied as such.
Chassaing
C
C
Intervet Innovation, Schwabenheim, Germany. christophe.chassaing@intervet.com
Berger
M
M
Heckeroth
A
A
Ilg
T
T
Jaeger
M
M
Kern
C
C
Schmid
K
K
Uphoff
M
M
D000284:Administration, Oral; D000818:Animals; D000871:Anthelmintics / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D002219:Carbamates / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D002645:Chickens; D004355:Drug Stability; D004386:Duodenum / Q000378:metabolism; D005273:Fenbendazole / Q000097:blood; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism; D007583:Jejunum / Q000378:metabolism; D009815:Oesophagostomum / Q000187:drug effects; D011355:Prodrugs / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D012995:Solubility; D013329:Structure-Activity Relationship; D013552:Swine; D019155:Veterinary Drugs / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D014867:Water
D000871:Anthelmintics; D001562:Benzimidazoles; D002219:Carbamates; D011355:Prodrugs; D019155:Veterinary Drugs; D014867:Water; D005273:Fenbendazole