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Population pharmacokinetics of pyrazinamide in elephants

Zhu, M ; Maslow, J.N ; Mikota, S.K ; Isaza, R ; Dunker, F ; Riddle, H ; Peloquin, C.A

Journal of veterinary pharmacology and therapeutics, 2005-10, Vol.28 (5), p.403-409 [Periódico revisado por pares]

Oxford, UK: Blackwell Science Ltd

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Título:
Population pharmacokinetics of pyrazinamide in elephants
Autor: Zhu, M ; Maslow, J.N ; Mikota, S.K ; Isaza, R ; Dunker, F ; Riddle, H ; Peloquin, C.A
Assuntos: absorption ; Administration, Oral ; Administration, Rectal ; Animals ; antimicrobial agents ; Antitubercular Agents - administration & dosage ; Antitubercular Agents - pharmacokinetics ; Antitubercular Agents - therapeutic use ; Area Under Curve ; dosage ; drug delivery systems ; drug therapy ; Elephants - metabolism ; Elephas maximus ; Female ; food deprivation ; Loxodonta africana ; Male ; Mycobacterium tuberculosis ; Mycobacterium tuberculosis - pathogenicity ; nonlinear models ; oral administration ; pharmacokinetics ; pyrazinamide ; Pyrazinamide - administration & dosage ; Pyrazinamide - pharmacokinetics ; Pyrazinamide - therapeutic use ; rectal administration ; rectum ; tuberculosis ; Tuberculosis, Pulmonary - blood ; Tuberculosis, Pulmonary - drug therapy ; Tuberculosis, Pulmonary - veterinary
É parte de: Journal of veterinary pharmacology and therapeutics, 2005-10, Vol.28 (5), p.403-409
Notas: ArticleID:JVP670
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SourceType-Scholarly Journals-1
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Descrição: This study was undertaken to characterize the population pharmacokinetics (PK), therapeutic dose, and preferred route of administration for pyrazinamide (PZA) in elephants. Twenty-three African (Loxodonta africana) and Asian (Elephas maximus) elephants infected with or in contact with others culture positive for Mycobacterium tuberculosis were dosed under treatment conditions. PZA was dosed daily at 20-30 mg/kg via oral (fasting or nonfasting state) or rectal (enema or suppository) administration. Blood samples were collected 0-24 h postdose. Population PK was estimated using nonlinear mixed effect modeling. Drug absorption was rapid with T(max) at or before 2 h regardless of the method of drug administration. C(max) at a mean dose of 25.6 (+/-4.6) mg/kg was 19.6 (+/-9.5 microgram/mL) for PZA given orally under fasting conditions. Under nonfasting conditions at a mean dose of 26.1 +/- 4.2 mg/kg, C(max) was 25% (4.87 +/- 4.89 microgram/mL) and area under concentration curve (AUC) was 30% of the values observed under fasting conditions. Mean rectal dose of 32.6 +/- 15.2 mg/kg yielded C(max) of 12.3 +/- 6.3 microgram/mL, but comparable AUC to PZA administered orally while fasting. Both oral and rectal administration of PZA appeared to be acceptable and oral dosing is preferred because of the higher C(max) and lower inter-subject variability. A starting dose of 30 mg/kg is recommended with drug monitoring between 1 and 2 h postdose. Higher doses may be required if the achieved C(max) values are below the recommended 20-50 microgram/mL range.
Editor: Oxford, UK: Blackwell Science Ltd
Idioma: Inglês

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Population pharmacokinetics of pyrazinamide in elephants

Zhu, M ; Maslow, J.N ; Mikota, S.K ; Isaza, R ; Dunker, F ; Riddle, H ; Peloquin, C.A

Oxford, UK: Blackwell Science Ltd

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