The Rumen as a Pharmacokinetic Compartment

Bogan, J. A.; Marriner, S. E.

doi:10.1007/978-94-009-3319-4_10

Cited by 14 publications

(10 citation statements)

References 14 publications

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“…In this latter study, products were not identified, but o-demethylation seems a probable reaction (Prins, 1987). Weak bases, such as TMP (pK, 7.6) and AP (pKa 6.7 and 7.8), should pass the blood-reticulorumen wall barrier after systemic administration (Bogan & Marriner, 1987; Dobson, 1967). As demonstrated in the present study, both drugs were detected in rumen fluid after i.v.…”

Section: Effects Of Tick-borne Fever On IV Pharmacokinetics Of Ap Amentioning

confidence: 89%

“…After oral administration, weak bases take some time to reach maximum concentrations in the plasma of ruminants. For example, experiments in sheep with levamisole (pK, 8.0), a base of high lipid and water solubility, showed that maximum plasma concentrations were reached 4-6 h after drug administration, whereas in dogs T,,, was about 0.5 h (Bogan & Marriner, 1987). For drugs which are poorly soluble in rumen contents, the time to maximum concentration will be longer due to slower passage of drug particles from the rumen.…”

Section: Effects Of Tick-borne Fever On IV Pharmacokinetics Of Ap Amentioning

confidence: 99%

“…Feeding can affect TMP availability (Groothuis & van Miert, 1987), whereas cellulose has a high capacity for drug binding (Bogan & Marriner, 1987). It is probable that drug binding occurs in the rumen and although the drug may be released on cellulose digestion, this will also serve to delay the absorptive process.…”

Section: Effects Of Tick-borne Fever On IV Pharmacokinetics Of Ap Amentioning

confidence: 99%

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Some pharmacokinetic data of aditoprim and trimethoprim in healthy and tick‐borne fever infected dwarf goats

Knoppert¹,

Nijmeijer²,

Duin³

et al. 1988

Vet Pharm & Therapeutics

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Aditoprim (AP) is a new dihydrofolate reductase inhibitor, which is structurally related to trimethoprim (TMP). The pharmacokinetics of AP (10 mg/kg) and TMP (20 mg/kg) were assessed in healthy dwarf goats. Therapeutic efficacy against rickettsial infections was tested in tick-borne fever (TBF) infected goats. The animals were given TMP (n = 5) or AP (n = 5) by i.v. injection, and subsequently the drugs were administered orally (same groups, similar doses). Finally, both groups were infected with TBF and the i.v. experiment was repeated. Plasma concentration-time curves for both drugs followed first-order two-compartment decay. For TMP, mean t1/2 beta +/- SEM (h) was 0.84 +/- 0.06 (i.v. control) and 0.90 +/- 0.06 (i.v. infected), respectively, whereas for AP values of 8.00 +/- 0.31 (i.v. control) and 10.28 +/- 0.67 (i.v. infected) were obtained (P less than 0.05). Mean Vd beta +/- SEM values (l/kg) were 3.84 +/- 0.27 (i.v. control) and 4.07 +/- 0.85 (i.v. infected) for TMP (NS) and 7.02 +/- 0.63 vs 9.29 +/- 0.21 (P less than 0.05) for AP. After i.v. injection, rumen fluid concentrations of AP were significantly (P less than 0.05) higher and more persistent than those of TMP. For AP, the plasma and rumen fluid concentrations at 3 h were 1.20 +/- 0.06 micrograms/ml and 0.85 +/- 0.17 microgram/ml, respectively. After oral administration of TMP, Cmax in plasma was 0.12 +/- 0.01 microgram/ml and the maximum was reached after 1.2 +/- 0.16 h; systemic bioavailability (F) was 10.3% (relative to AUC i.v.). Oral treatment with AP resulted in a Cmax value of 0.21 +/- 0.02 microgram/ml with Tmax of 22.5 +/- 1.65 h and a F value of 71%. Based on WBC, serum ALP and rectal temperature responses, it was concluded that both TMP and AP were inactive against Ehrlichia phagocytophila.

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Section: Effects Of Tick-borne Fever On IV Pharmacokinetics Of Ap Amentioning

confidence: 89%

Section: Effects Of Tick-borne Fever On IV Pharmacokinetics Of Ap Amentioning

confidence: 99%

Section: Effects Of Tick-borne Fever On IV Pharmacokinetics Of Ap Amentioning

confidence: 99%

See 1 more Smart Citation

Some pharmacokinetic data of aditoprim and trimethoprim in healthy and tick‐borne fever infected dwarf goats

Knoppert¹,

Nijmeijer²,

Duin³

et al. 1988

Vet Pharm & Therapeutics

View full text Add to dashboard Cite

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“…These differences may be associated with prolonged absorption time of the drug from fed group compared with the fasted group. The physical form and quality of diet may affect the digestibility, flow rate into the gastrointestinal tract, the binding ability of content to the drug and the quality, quantity and reductive capacity of the gastrointestinal microflora [21] .…”

Section: Discussionmentioning

confidence: 99%

Keçilerde Albendazolün Plazma Dağılımına Aç Bırakmanın Etkisi

Karademir¹,

GÖKBULUT²,

BOYACIOĞLU³

2015

Kafkas Univ Vet Fak Derg

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This study was designed to investigate the effect of fasting on the plasma disposition of albendazole (ABZ) in goats following oral administration. A total of 10 goats, aged 5-6 months were used in this study. The animals were allocated into two groups (fasted and fed groups) of five animals each. ABZ was administered orally to animals in two groups at 10 mg/kg bodyweight. Heparinize blood samples were collected between 1 h and 144 h after treatment and the plasma samples were analysed by high performance liquid chromatography for ABZ, active albendazole sulphoxide (ABZSO) and inactive albendazole sulphone (ABZSO2) metabolites. ABZ is not detected and ABZSO and ABZSO2 metabolites were present in the samples of fed and fasted animals. Feeding was significantly enhanced the plasma concentration of the ABZSO and ABZSO2 metabolites. The area under the curve (AUC) and half-life (t1/2) of both metabolites were significantly larger and longer in fed compared to fasted animals, respectively. Moreover the maximum plasma concentration (Cmax: 1.06±0.17 µg/ml) of ABZSO2 was also significantly higher in fed group compared with the fasting group (0.72±0.20 µg/ml). The changes in plasma kinetics, reflecting an altered quantitative gastrointestinal absorption or metabolism, were reflected in increased availability of ABZ metabolites in the plasma of fed goats. This could be a strategy to extend the exposure of parasites to the more active metabolite of ABZ and thus to improve the efficacy in goats. Keywords: Benzimidazoles, Albendazole, Pharmacokinetics, Fasting, Goat Keçilerde Albendazolün Plazma Dağılımına Aç Bırakmanın Etkisi ÖzetBu çalışma keçilere albendazolün (ABZ) ağız yolu ile uygulanmasını takiben aç bırakmanın etkisini araştırmak amacı ile yapılmıştır. Çalışmada 5-6 aylık yaşta 10 keçi kullanılmıştır. Hayvanlar her grupta (aç ve tok) beş keçi olacak şekilde iki gruba ayrılmıştır. Her iki gruptaki hayvanlara ABZ 10 mg/kg dozda ağız yolu ile uygulanmıştır. Heparinize kan örnekleri ilaç uygulanmasından sonra 1 saat ile 144. saat arasında toplanmıştır ve plazma örnekleri ABZ, aktif albendazol sülfoksit (ABZSO) ve inaktif albendazol sülfon (ABZSO2) metabolitleri için yüksek basınçlı sıvı kromatografisi ile analiz edildi. Aç ve tok hayvanlardan toplanan örneklerde ABZ tespit edilememiş, ABZSO ve ABZSO2 metabolitleri bulunmuştur. Besleme ABZSO ve ABZSO2 metabolitlerinin plazma konsantrasyonunu anlamlı şekilde artırmıştır. Beslenen gruptaki hayvanlarda her iki metabolitin eğri altı alanı (EAA) ve yarılanma ömrü (t1/2) anlamlı bir şekilde geniş ve uzun bulunmuştur. ABZSO2'un doruk plazma yoğunluğu (Ydoruk: 1.06±0.17 µg/ml) beslenen gruptaki hayvanlarda, aç bırakılan gruptaki hayvanlardan (Ydoruk: 0.72±0.20 µg/ml) anlamlı birşekilde yüksek bulunmuştur. Nicel gastrointestinal emilim yada metabolizmada ki değişimleri yansıtan plazma kinetiğindeki değişimler beslenen keçilerin plazmasında ABZ metabolitlerinin yararlanımının arttığının göstergesidir. Bu durum keçilerde ABZ'un aktif metabolitlerine parazitin daha fazla maruz...

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“…However, concentrations in rumen fluid may not be representative of total concentration in the rumen, because drug fraction bound to the solid phase is not detected (Sutter et al ., 1993) and fluoroquinolones present low water solubility at ruminal pH (Ashby et al ., 1995; Gips & Soback, 1999). Cellulose and other macromolecules present in the rumen content have a high capacity for drug binding and this could influence the pharmacokinetics of some drugs (Bogan & Marriner, 1987). Binding of NF to bivalent cations present in the rumen environment may also be involved (Janknegt, 1990).…”

Section: Discussionmentioning

confidence: 99%

Influence of ruminal distribution on norfloxacin pharmacokinetics in adult sheep

González

Andrés

Nieto

et al. 2001

Vet Pharm & Therapeutics

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Norfloxacin (NF) ruminal distribution after intravenous (i.v.), intramuscular (i.m.) and oral (p.o.) administration was determined in order to assess the influence of the rumen on the pharmacokinetic behaviour of NF in sheep. Norfloxacin concentrations in rumen were detected after i.v. and i.m. administrations between 4 and 48 h in all animals studied. The experimental distribution ratios after i.v. and i.m. administration expressed as area under the concentration-time curve ratios AUC(rumen)/AUC(plasma) were 0.24 and 0.39, respectively, and thus lower than corresponding predicted value of 5.06. Apparently, drug persisted in the rumen content longer than in plasma. The experimental mean residence time ratios MRT(rumen)/MRT(plasma) after i.v. and i.m. administrations were 2.33 and 1.66, respectively. After p.o. administration, NF concentrations in the rumen content were extremely high compared with the respective plasma concentrations, resulting in mean peak concentrations ratio C(max-rumen)/C(max-plasma) of 383.66 and AUC(rumen)/AUC(plasma) experimental ratio of 402.32. This value was considerably higher (approximately 79 fold) than the predicted distribution ratio of 5.06. Our results suggest that the limited p.o. bioavailability of NF in ruminants could not be attributed to ruminal degradation.

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The Rumen as a Pharmacokinetic Compartment

Cited by 14 publications

References 14 publications

Some pharmacokinetic data of aditoprim and trimethoprim in healthy and tick‐borne fever infected dwarf goats

Some pharmacokinetic data of aditoprim and trimethoprim in healthy and tick‐borne fever infected dwarf goats

Keçilerde Albendazolün Plazma Dağılımına Aç Bırakmanın Etkisi

Influence of ruminal distribution on norfloxacin pharmacokinetics in adult sheep

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