The disposition of theophylline in camels after intravenous administration

Wasfi, I.A.; Elghazali, M.; Boni, N. S.; Hadi, A. A. A.; Alhadrami, Ghaleb; Almuhrami, A. M.; Alkatheeri, N. A.; Barezaiq, I.M.; Agha, Bushra; Wajid, S. A.

doi:10.1046/j.1365-2885.1999.00220.x

Cited by 3 publications

(4 citation statements)

References 27 publications

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“…The higher V d of MKC may be attributed to intrappment of MKC in the gastrointestinal tract (17,18). However, MKC is characterized by a short half-life and short MRT which could be attributed to the rapid metabolism of MKC (19) resulting from its ability to stimulate the excretion of bile and hence accelerate its own elimination (20). The low values for bioavailability and C max of MKC may be due to the high presystemic elimination of this drug (21).…”

Section: Discussionmentioning

confidence: 99%

Bioavailability and hypoglycemic activity of the semisynthetic bile acid salt, sodium 3α,7α-dihydroxy-12-0X0-5β-cholanate, in healthy and diabetic rats

Mikov

Boni

Al‐Salami

et al. 2007

Eur. J. Drug Metabol. Pharmacokinet.

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Previous studies in our laboratory have shown that the semisynthetic bile acid derivative, sodium 3alpha,7alpha-dihydroxy-12-oxo-5beta-cholanate (MKC), has hypoglycemic activity. The aim of this study was to investigate the relationship between the pharmacokinetics and hypoglycemic activity of MKC in healthy and diabetic rats. Groups of healthy and alloxan-induced diabetic rats were dosed intravenously (i.v.) and orally with MKC (4 mg/kg). Blood samples were taken before administration of the dose and at 20, 40, 60, 80, 120, 150, 180, 210 and 240 minutes post-dose. MKC serum concentration was measured by HPLC, and pharmacokinetic parameters determined using the WinNonlin program. The absolute bioavailability of MKC was found to be low in healthy and diabetic rats (29 and 23% respectively) and was not significantly different between the two groups. Mean residence time (MRT), volume of distribution (Vd) and half-life (t1/2) of MKC after oral administration were significantly lower in diabetic than in healthy rats (21, 31 and 29% respectively). After the i.v. dose, the change in blood glucose concentration was not significant in either healthy or diabetic rats. After the oral dose, the decrease in blood glucose concentration was significant, reaching a maximum decrease from baseline of 24% in healthy rats and 15% in diabetic rats. The results suggest that a first-pass effect is crucial for the hypoglycemic activity of MKC, indicating that a metabolite of MKC and/or interference with metabolism and glucose transport is responsible.

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Section: Discussionmentioning

confidence: 99%

Bioavailability and hypoglycemic activity of the semisynthetic bile acid salt, sodium 3α,7α-dihydroxy-12-0X0-5β-cholanate, in healthy and diabetic rats

Mikov

Boni

Al‐Salami

et al. 2007

Eur. J. Drug Metabol. Pharmacokinet.

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“…We could not detect any of the theophylline (xanthine base) metabolites as a result of further theophylline metabolism. This, however, is in contrast with earlier reports that theophylline was metabolized to 1,3 dimethyl uric acid and 3 methyl xanthine in horses (Harkins et al ., 1998) and to caffeine in camels (Wasfi et al ., 1999, 2000b). This may be attributable to several reasons: (1) the volume of urine sample used was 5–10 mL; (2) the concentration of theophylline as Et metabolite was very small; (3) the elimination of theophylline via caffeine metabolism was very low 0.01% of the administered theophylline dose (Wasfi et al ., 1999).…”

Section: Discussionmentioning

confidence: 99%

“…Perviously N‐dealkylation of theophylline (xanthine bronchdilator) has been reported and that cytochrome P450 (CYP) ΙAE catalysed 80–90% of theophylline N‐dealkylation in vitro (Robson et al ., 1988; Rasmussen et al ., 1995). In horses and camels, theophylline is persumably metabolized by CYP ΙAE and CYP 2EI (Harkins et al ., 1998; Wasfi et al ., 1999). The same enzymes are, persumably, responsible for the major route of Et N‐dealkylation in camel.…”

Section: Discussionmentioning

confidence: 99%

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The pharmacokinetics, metabolism and urinary detection time of etamiphylline in camels after intramuscular administration

Elghazali¹,

Wasfi²,

Katheeri³

et al. 2002

Vet Pharm & Therapeutics

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The pharmacokinetics of etamiphylline were determined after an intramuscular (i.m.) dose of 3.5 mg/kg body weight in six healthy camels. Furthermore, the metabolites and drug detection time were evaluated. The data obtained median and (range) were as follows: the terminal elimination half-life (t(1/2 beta), h) was 3.04 (2.03-3.62); apparent total body clearance (Cl/F, L/h/kg) was 1.27 (0.74-2.99); the apparent volume of distribution at steady state (V(ss)/F, L/kg) was 4.94 (3.57-12.54); and renal clearance (Cl(r), L/h/kg) determined in two camels was 0.005 and 0.004, respectively. The detection time of etamiphylline in urine after an i.m. dose of 3.5 mg/kg body weight ranged between 12 and 13 days. Three etamiphylline metabolites were tentatively identified in camels urine: The first one desethyletamiphylline was the main metabolite and resulted from N-deethylation of etamiphylline had a molecular weight of 251, and was detected in urine for about 13-14 days. Theophylline (molecular weight 180) was the second metabolite and resulted from ring N-dealkylation of etamiphylline. It was present in small amounts and was detected for about 5 h after drug administration in urine. The third metabolite, possibly resulted from demethylation of etamiphylline, had a molecular weight of m/z 265, and was present in small amounts and was detected in urine for about 5 h after drug administration.

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Wasfi

Hadi

Elghazali

et al. 2003

Veterinary Research Communications

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The pharmacokinetics of diphenhydramine (DPHM) was compared in camels (n = 8) and horses (n = 6) following intravenous (i.v.) administration of a dose of 0.625 mg/kg body weight. In addition, the metabolism and urinary detection time of DPHM was evaluated in camels. The data obtained (median and range in brackets) in camels and horses, respectively, were as follows. The terminal elimination half lives (h) were 1.58 (1.13-2.58) and 6.11 (4.80-14.1), and the total body clearances (L/h per kg) were 1.42 (1.13-1.74) and 0.79 (0.66-0.90). The volumes of distribution at steady state (L/kg) were 2.38 (1.58-4.43) and 5.98 (4.60-8.31) and the volumes of the central compartment of the two compartment pharmacokinetic model were 1.58 (0.80-2.54) and 2.48 (1.79-3.17). All the pharmacokinetic parameters in camels were significantly different from those of horses. Five metabolites of DPHM were tentatively identified in the camel's urine. Two metabolites, diphenylmethoxyacetic acid and 1-(4-hydroxyphenyl)-phenylmethoxyacetic acid, were present in the acid fraction. Two metabolites, desamino-DPHM and diphenylmethanol, were identified in the basic fraction, in addition to DPHM itself, which was present mainly as a conjugate. Even after enzymatic hydrolysis, DPHM could be detected for up to 24 h in camels after an i.v. dose of 0.625 mg/kg body weight.

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The disposition of theophylline in camels after intravenous administration

Cited by 3 publications

References 27 publications

Bioavailability and hypoglycemic activity of the semisynthetic bile acid salt, sodium 3α,7α-dihydroxy-12-0X0-5β-cholanate, in healthy and diabetic rats

Bioavailability and hypoglycemic activity of the semisynthetic bile acid salt, sodium 3α,7α-dihydroxy-12-0X0-5β-cholanate, in healthy and diabetic rats

The pharmacokinetics, metabolism and urinary detection time of etamiphylline in camels after intramuscular administration

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