A One-Sample Method for Antipyrine Clearance Determination in Rats

Pilsgaard, Helle; Poulsen, Henrik Enghusen

doi:10.1159/000137999

Cited by 45 publications

(15 citation statements)

References 11 publications

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“…dose/AUC, where AUC is the area under the curve) following serial blood sampling. Total clearance of P (CIT) was determined from the concentration (C,) of P in the 6-h plasma sample, the dose of P administered ( D ) (50 or 300mg/kg), the assumed volume of distribution (V) and the sampling time (t), according to the following equation (Pilsgard and Poulsen 1984):…”

Section: Calculation Of Pharmacokinetic Parametersmentioning

confidence: 99%

Effect of malaria infection on the pharmacokinetics of paracetamol in rat

et al. 1994

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1. Paracetamol (P; 50 and 300 mg/kg i.v.) was administered to the control and malaria-infected (MI) male Wistar rat in order to assess the effect of MI on the metabolism of paracetamol to its glucuronide (PG) and sulphate (PS) conjugates and their excretion in urine. 2. At a dose of 50 mg/kg, neither total clearance (ClT) (controls, 20.3 +/- 0.5; MI, 19.9 +/- 0.9, ml/min/kg; mean +/- SD, p > 0.05) nor the renal clearance of P (ClR) were affected by MI. Although the formation clearance of PG (Clf PG) was decreased by about 40% (controls, 6.6 +/- 1.1; MI, 3.9 +/- 0.9, ml/min/kg, p < 0.05), the formation clearance of PS (Clf PS) was increased by 30% in the MI rat (controls, 8.8 +/- 0.9; MI, 11.2 +/- 1.7, ml/min/kg, p < 0.05), and therefore Clm (controls, 19.7 +/- 0.5; MI, 19.2 +/- 0.8, ml/min/kg, p > 0.05) was unchanged by MI. 3. At a dose of 300 mg/kg, MI produced a significant decrease in the total clearance of P (ClT) (controls, 16.9 +/- 1.0; MI, 11.9 +/- 0.9, ml/min/kg, p < 0.05), metabolic clearance (Clm) (controls, 15.9 +/- 1.4; MI, 11.3 +/- 0.9, ml/min/kg, p < 0.05) and the formation clearance of PG (Clf PG) (controls, 7.9 +/- 1.3; MI, 4.7 +/- 1.5, ml/min/kg, p < 0.05) without affecting Clf PS and ClR of P. 4. These findings indicate that MI impairs the glucuronidation of paracetamol in rat in vivo at both the low and high doses of P. Increased sulphate formation appeared to compensate for decreased glucuronidation at the lower dose.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Calculation Of Pharmacokinetic Parametersmentioning

confidence: 99%

Effect of malaria infection on the pharmacokinetics of paracetamol in rat

et al. 1994

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“…(1982) calculated the antipyrine clearance based on a single sample only. This method, however, requires that the vol ume of distribution be either simply assumed or calculated from equations relating total body water to age, body mass or gender (Pilsgaard and Poulsen 1984). Dan ho f et a1.…”

Section: Resultsmentioning

confidence: 99%

Evaluation of Simplified Antipyrine Test in Calves

Janus¹,

Suszycka²,

Muszczynski³

1997

Acta Vet. Brno

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The purpose of this study was to test a modification of antipyrine test in calves. The experiment was carried out on 10 calves (bulls of black and white breed). Each subject received on days 10 and 20 of life. respectively. 15 mg.kg· l body mass of antipyrine as an intravenous bolus injection. followed by its oral administration "in substantia" in gelatin capsules 48 hours later. The concentrations of antipyrine in their saliva were repeatedly determined. Pharmacokinetics of antipyrine was followed in each subject (according to a one-compartment open model) using five modifications: a complete study (A). and four abbreviated studies. i.e using the 4. 8 and 12 h saliva collection times (B). the 4 and 8 h collection times (C), further the 4 and 12 h (D). and finally the 8 and 12 h saliva collection times (E). Correlational analysis was used to compare the substance kinetics from the complete set of data obtained from all saliva collections with the results using each of the abbreviated approaches.Based on the complete kinetics studies, mean variables for antipyrine were as follows: half-life In conclusion. we demonstrated that antipyrine pharmacokinetic parameters in calves can be determined with reasonable precision using a two-point or three-point saliva sampling procedure following a single oral dose. Moreover. this simplified sampling method can be used for largescale investigations. where estimation of hepatic mixed function oxygenases (MFO) activity is needed.Antipyrine, intravenous and oral administration. MFO system, calves

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“…Five hours later the animals were exsanguinated, 3-ml blood samples were taken and liv ers were removed blotted and weighed. The antipyrine clearance was calculated using the one-sample method [14], Serum antipyrine concentrations were measured by HPLC [15], Amphotericin B' was from Sqibb Flevdcn (Mu nich, Germany) and contains 50 mg amphotericin B and 41 mg sodium deoxycholate as a detergent per vial. Sodium dcoxycholate was purchased from Sig ma.…”

Section: Measurement O F Antipyrine Clearancementioning

confidence: 99%

Influence of Amphotericin B Treatment Duration on Hepatic Microsomal Enzyme Function in Rats

Inselmann¹,

Voss²,

Kunigk

et al. 1997

Pharmacology

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The influence of amphotericin B on various cytochrome P450-dependent mixed-function oxidases, antipyrine clearance and glucose-6-phosphatase was investigated in rats treated daily with deoxycholate amphotericin B (3 mg/kg body weight, intravenously) either for 1 or 4 days. Enzyme activity was measured ex vivo in hepatic microsomes. Following amphotericin B plus deoxycholate application for 1 day, ethoxycoumarin-O-deethylase activity decreased significantly whereas microsomal cytochrome P450 concentration, cytochrome c reductase activity, antipyrine clearance and glucose-6-phosphatase activity did not change significantly. In contrast, following application of amphotericin B plus deoxycholate for 4 days the cytochrome P450 concentration was reduced by 50% (p < 0.05) as well as ethoxycoumarin-O-deethylase activity, antipyrine clearance and glucose-6-phosphatase activity: ethoxycoumarin-O-deethylase 232 ± 68 pmol/ mg/min, control 442 ± 99 pmol/mg/min (p < 0.01); antipyrine clearance 0.56 ± 0.21 ml/min, control 0.96 ± 0.18 ml/min (p < 0.01), and glucose-6-phosphatase 193 ± 28 mU/mg, control 351 ± 95 mU/mg (p < 0.05). Cytochrome c reductase activity did not decrease significantly. Besides an increase in cytochrome c reductase activity, sodium deoxycholate (a vehicle of amphotericin B) alone induced no significant changes. Microsomal protein related to liver wet weight was significantly reduced by 50% (p < 0.01) only in animals treated for 4 days with amphotericin B plus deoxycholate. The results show that a 1-day treatment of rats with amphotericin B decreases ethoxycoumarin-O-deethylase activity, whereas the hepatic microsomal cytochrome P450 content, cytochrome c reductase and glucose-6-phosphatase activity did not change. Amphotericin B given for 4 days significantly decreases hepatic microsomal enzyme function. The inhibitory effect of amphotericin B on hepatic cytochrome P450 may be due to inhibition of hepatic protein synthesis.

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A One-Sample Method for Antipyrine Clearance Determination in Rats

Cited by 45 publications

References 11 publications

Effect of malaria infection on the pharmacokinetics of paracetamol in rat

Effect of malaria infection on the pharmacokinetics of paracetamol in rat

Evaluation of Simplified Antipyrine Test in Calves

Influence of Amphotericin B Treatment Duration on Hepatic Microsomal Enzyme Function in Rats

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