Oral bioavailability and in vitro stability of pivampicillin, bacampicillin, talampicillin, and ampicillin in horses.
OBJECTIVE
To determine the oral bioavailabilities of 3 ampicillin esters (pivampicillin, bacampicillin, and talampicillin) and ampicillin sodium, and to determine in vitro stability of the ampicillin esters in ileal contents (pH 8.3 to 8.5).


METHODS
A crossover design to administer the 4 drugs orally, and ampicillin i.v. to all horses in the study.


METHODS
4 healthy adult horses.


METHODS
The drugs were administered intragastrically to the horses at a dosage equimolar to 15 mg of ampicillin/kg of body weight. Also, ampicillin sodium was administered i.v. at the same dosage. Blood samples were taken up to 12 hours after drug administration, and ampicillin concentrations in plasma were determined. For the in vitro study, the ampicillin esters were incubated at 37 C in ileal contents obtained from ponies with cecal fistulas. After incubation, the remaining intact ester and the formed ampicillin were measured.


RESULTS
Absolute oral bioavailability was 31, 39, 23, and 2% for pivampicillin, bacampicillin, talampicillin, and ampicillin sodium, respectively. In the in vitro study, 90% decomposition of the ester took place in 30, 60, and 5 minutes, for pivampicillin, bacampicillin, and talampicillin, respectively.


CONCLUSIONS
Pivampicillin and bacampicillin are promising candidates for oral antibiotic treatment of horses. The rapid decomposition of ampicillin esters is caused by chemical hydrolysis at the high pH of equine ileal contents.
Ensink
J M
JM
Department of General and Large Animal Surgery, Utrecht University, The Netherlands.
Vulto
A G
AG
van Miert
A S
AS
Tukker
J J
JJ
Winkel
M B
MB
Fluitman
M A
MA
D000284:Administration, Oral; D000667:Ampicillin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics*; D000818:Animals; D001682:Biological Availability; D018592:Cross-Over Studies; D004355:Drug Stability; D005260:Female; D006207:Half-Life; D006736:Horses; D007408:Intestinal Absorption; D008297:Male; D008657:Metabolic Clearance Rate; D009919:Orchiectomy; D010406:Penicillins / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D010917:Pivampicillin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D013626:Talampicillin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*
D010406:Penicillins; D010917:Pivampicillin; D013626:Talampicillin; D000667:Ampicillin; C011674:bacampicillin