New Calculation Method for Mean Apparent Drug Volume of Distribution and Application to Rational Dosage Regimens

Chiou, Win L.

doi:10.1002/jps.2600680843

Cited by 169 publications

(93 citation statements)

References 10 publications

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“…The harmonic mean method was employed to calculate the mean values of V ss (Chiou, 1979), terminal half-life (Eatman et al, 1977), and CL (Chiou, 1980). Glomerular filtration rate was calculated by measuring creatinine clearance (CL CR ) assuming that kidney function was stable during the 8-hr experimental period.…”

Section: Methodsmentioning

confidence: 99%

Effects of Acute Renal Failure on the Pharmacokinetics of Chlorzoxazone in Rats

Moon¹,

Lee²,

Chung³

et al. 2003

Drug Metab Dispos

111

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ABSTRACT:The purpose of this study is to report the changes of CYP2E1, CYP1A2, CYP2B1/2, CYP2C11, CYP3A23, and CYP3A2 expression and pharmacokinetics and tissue distribution of chlorzoxazone (CZX) and 6-hydroxychlorzoxazone (OH-CZX) in rats with acute renal failure induced by uranyl nitrate (U-ARF), and the role of CYP3A23 and CYP3A2 in the formation of OH-CZX in rats with U-ARF. In rats with U-ARF, CYP2C11 decreased to 20% of control, whereas CYP2E1 and CYP3A23 increased 2.3 and 4 times, respectively, compared with control. But expression of CYP1A2 and CYP2B1/2 was not changed by U-ARF. After i.v. administration of CZX at a dose of 20 mg/kg to rats with U-ARF, the areas under the plasma concentration-time curve from time 0 to time infinity (AUCs) of CZX and OH-CZX were significantly smaller and greater, respectively, than those in control rats. In rats with U-ARF, CZX was below the detection limit at 120 min in all rat tissues studied, whereas it was detected in all tissues of control rats at both 30 and 120 min. However, in control rats, OH-CZX was below the detection limit at both 30 and 120 min in all rat tissues except kidney, whereas it was detected in all tissues of rats with U-ARF at both 30 and 120 min. Based on results from supporting experiments with DDT and 2,2-bis(4-chlorophenyl)1,1-dichloroethylene treatment of rats, the contribution of CYP3A23 and CYP3A2 to the enhanced formation of OH-CZX in rats with U-ARF is likely to be negligible.

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Section: Methodsmentioning

confidence: 99%

Effects of Acute Renal Failure on the Pharmacokinetics of Chlorzoxazone in Rats

Moon¹,

Lee²,

Chung³

et al. 2003

Drug Metab Dispos

111

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“…The following pharmacokinetic parameters were estimated (Gibaldi and Perrier, 1982): area under the plasma concentration-time curve from time 0 to time infinity (AUC), time-averaged total body clearance (CL), area under the first moment of plasma concentration-time curve, mean residence time (MRT), apparent volume of distribution at steady-state (V ss ) and time-averaged renal (CL R ) and nonrenal (CL NR ) clearances (Kim et al, 1993). The mean values of each clearance (Chiou, 1980), V ss (Chiou, 1979) and terminal half-life (Eatman et al, 1977) were estimated by the harmonic mean method.…”

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confidence: 99%

Pharmacokinetics and Pharmacodynamics of Intravenous Azosemide in Mutant Nagase Analbuminemic Rats

Kim

Lee²,

Kim³

et al. 2003

Drug Metab Dispos

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ABSTRACT:This paper reports 1) the increase in expression of CYP1A2 in mutant Nagase analbuminemic rats (NARs), 2) the role of globulin binding of azosemide in circulating blood in its urinary excretion and hence its diuretic effects in NARs, and 3) the significantly faster renal (CL R ) and nonrenal (CL NR ) clearances of azosemide in NARs. Azosemide (mainly metabolized via CYP1A2 in rats), 10 mg/kg, was intravenously administered to control rats and NARs. Northern and Western blot analyses revealed that the expression of CYP1A2 increased ϳ3.5-fold in NARs as compared with control. The plasma protein binding of azosemide in control rats and NARs was 97.9 and 84.6%, respectively. In NARs, plasma protein binding (84.6%) was due to binding to ␣-(82.6%) and ␤-(68.9%) globulins. In NARs, the amount of unchanged azosemide excreted in 8-h urine was significantly greater (37.7 versus 21.0% of intravenous dose) than that in control rats due to an increase in intrinsic renal active secretion of azosemide. Accordingly, the 8-h urine output was significantly greater in NARs. The area under the plasma concentration-time curve of azosemide was significantly smaller (505 versus 2790 g ⅐ min/ml) in NARs because of markedly faster CL R (7.36 versus 0.772 ml/min/kg, secondary to a significant increase in urinary excretion of azosemide and intrinsic renal active secretion). Additionally, CL NR was significantly faster (12.4 versus 3.05 ml/min/kg, because of ϳ3.5 fold increase in CYP1A2) in NARs compared with control. Based on in vitro hepatic microsomal studies, the intrinsic M1 [a metabolite of azosemide; 5-(2-amino-4-chloro-5-sulfamoylphenyl)-tetrazole] formation clearance was significantly faster (67.0% increase) in NARs than that in control rats, and this supports significantly faster CL NR in NARs. Renal sensitivity to azosemide was significantly greater in NARs than in control rats with respect to 8-h urine output (385 versus 221 ml/kg) and 8-h urinary excretions of sodium, potassium, and chloride. This study supports that in NARs, binding of azosemide to ␣-and ␤-globulins in circulating blood play an important role in its diuretic effects.Azosemide 1 [5-(4-chloro-5-sulfamoyl-2-thenylaminophenyl)-tetrazole] is a sulfonamide loop diuretic closely resembling furosemide in its diuretic action (Krück et al., 1978). Its main sites of action are both the cortical and medullary segments of the thick ascending limb of loop of Henle (Brater, 1979) where it inhibits water and solute reabsorption. It is used clinically in the treatment of edematous states and arterial hypertension; specific indications are cardiac and renal edema and ascites (Michel, 1992). Eleven metabolites of azosemide were found in rat urine and bile (Asano et al., 1984), but the diuretic effect of the drug does not require metabolism to an active metabolite (Greven, 1991).After i.v. administration of furosemide to mutant Nagase analbuminemic rats (NARs), an animal model for human familial analbuminemia, the diuretic effects of the drug (urine output and urinary e...

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“…The harmonic mean method was employed for the calculation of the mean values of V ss [11], terminal half-life [12], and Cl [13].…”

Section: Pharmacokinetic Analysismentioning

confidence: 99%

Pharmacokinetics of a new reversible proton pump inhibitor, YH1885, after intravenous and oral administrations to rats and dogs: hepatic first-pass effect in rats

Han

Kim

Yoo

et al. 1998

Biopharm. Drug Dispos.

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New Calculation Method for Mean Apparent Drug Volume of Distribution and Application to Rational Dosage Regimens

Cited by 169 publications

References 10 publications

Effects of Acute Renal Failure on the Pharmacokinetics of Chlorzoxazone in Rats

Effects of Acute Renal Failure on the Pharmacokinetics of Chlorzoxazone in Rats

Pharmacokinetics and Pharmacodynamics of Intravenous Azosemide in Mutant Nagase Analbuminemic Rats

Pharmacokinetics of a new reversible proton pump inhibitor, YH1885, after intravenous and oral administrations to rats and dogs: hepatic first-pass effect in rats

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