The assessment of fractional drug removal by extracorporeal dialysis

Lee, Ching-San C.

doi:10.1002/bdd.2510030207

Cited by 14 publications

(12 citation statements)

References 14 publications

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“…The proportion of the body pool of drug removed by a given period of hemodialysis (f) is calculated by the equation: f = [CLHD/(CLHD + CLb)] {1 -exp [-(CLHD + CLb)t/Vd)I}, where CLHD is the hemodialysis clearance of the drug, CLb.is the intrinsic body clearance of the drug, and t is the duration of hemodialysis (9,15). In a hypothetical anephric patient with a body weight of 60 kg, the Varca is expected to be 16.2 liters (i.e., 0.270 liters/kg) and v is 0.0469/h (Fig.…”

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confidence: 99%

Pharmacokinetics of cefmenoxime in patients with impaired renal function and in those undergoing hemodialysis

Konishi¹

1986

Antimicrob Agents Chemother

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The pharmacokinetics of cefmenoxime were studied after a single intravenous 1.0-g dose to 24 subjects grouped according to their renal functions. Creatinine clearance was above 85, 50 to 85, 10 to 50, and below 10 ml/min per 1.73 m2 in groups 1, 2, 3, and 4, respectively. Cefmenoxime obeyed two-compartment-model kinetics in all four groups. The volume of distribution based on the area under the serum concentration-time curve was renal function independent, the average value being 0.270 +/- 0.075 liters/kg. The elimination-phase half-life (t1/2 beta) was 0.82 +/- 0.30 h in group 1, 1.38 +/- 0.36 h in group 2, 3.32 +/- 1.82 h in group 3, and 7.60 +/- 1.28 h in group 4. Cumulative 24-h urinary excretion accounted for 65.5 +/- 7.6% of the dose in group 1 and for 7.50 +/- 3.72% in group 4. Recommendations for dosage adjustment in patients with renal insufficiency are proposed based on the data obtained in this study. The effect of hemodialysis on cefmenoxime pharmacokinetics was studied in six patients in group 4; hemodialysis shortened the average t1/2 beta from 7.60 +/- 1.28 to 4.19 +/- 1.66 h. It was estimated that in a hypothetical anephric subject with a body weight of 60 kg, 5-h hemodialysis would remove 28.2% of the drug present in the body at the start of hemodialysis.

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confidence: 99%

Pharmacokinetics of cefmenoxime in patients with impaired renal function and in those undergoing hemodialysis

Konishi¹

1986

Antimicrob Agents Chemother

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“…The same authors also calculated the hemodialysis clearance by a method identical to our equation 3: the reported values were 66.5 ± 13.2 ml/min for imipenem and 47.6 + 22.6 ml/min for cilastatin. Thus, the hemodialysis clearances of both imi- where CLHD is the hemodialysis clearance of the drug, CLb is the intrinsic body clearance of the drug, t is the duration of hemodialysis, and V is the volume of distribution (7,10). The volume of distribution of imipenem has been reported to be 0.23 to 0.31 liters/kg (2).…”

Section: Discussionmentioning

confidence: 99%

Removal of imipenem and cilastatin by hemodialysis in patients with end-stage renal failure

Konishi

Suzuki

Saruta

et al. 1991

Antimicrob Agents Chemother

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The removal of nimpenem and cilastatin by hemodialysis was studied in 14 (for imipenem) and 6 (for cilastatin) subjects. FoUowing intravenous infusion of imipenem and cilastatin at a combined concentration of 10 mg/kg of body weight, drug levels in plasma were determined serially during off-and on-hemodialysis periods, which were 2 and 4 h, respectively. The biexponential decay of the drug levels in plasma was evident in each subject for both imipenem and cilastatin. Hemodialysis accelerated the elimination of both imipenem and cilastatin: the mean elimination-phase half-life of imipenem was shortened from 200 to 78 min, and that of cilastatin was shortened from 445 to 115 min. Hemodialysis clearance of imipenem and cilastatin was calculated by five different methods, each with intrinsic assumptions. The mean hemodialysis clearance of niipenem was estimated to be 74.08 + 13.29 ml/min, and that of cilastatin was estimated to be 65.0 + 8.6 ml/min, after consideration of various methodological limitations. It was estimated that in a hypothetical anephric patient weighing 60 kg, a 4-h hemodialysis treatment would remove 54.8% of the imipenem and 62.9% of the cilastatin present in the body at the start of dialysis.

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“…Equation 34 was derived by Takki et al (1978) and Gwilt and Perrier (1978) on the basis of clearance and volume of distribution, while Lee (1982) suggested the use of rate constants (equation 34a).…”

Section: Fractional Drug Removalmentioning

confidence: 99%

“…Some considerations and simulations have been presented by Lee (1982), Gwilt (1981) and Gibson (1979). Dialysis of drugs 51 in a multicompartment system needs to be treated explicitly on a drug-by-drug and model-by-model basis, and therefore a general formula will not be presented.…”

Section: Fractional Drug Removalmentioning

confidence: 99%

“…Guidelines on which to base dosage regimens in ESRD patients can be found in a number of review articles (Bennett et al, 1980;Dettli, 1976;Gambertoglio, 1979). The pharmacokinetic effects of haemodialysis on drug removal have been reviewed and summarised (Gibson, 1979;Gwilt and Perrier, 1978;Knepshield et aI., 1973;Lee, 1982;Watanabe, 1977). During concomitant drug therapy, the removal of a drug by haemodialysis may be significant enough to require a dosage supplement to ensure adequate therapeutic efficacy.…”

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Drug Therapy in Patients Undergoing Haemodialysis

Lee

Marbury

1984

Clinical Pharmacokinetics

Self Cite

105

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Haemodialysis is utilised therapeutically as supportive treatment for end-stage renal disease (ESRD). In conjunction with haemodialysis therapy, ESRD patients frequently receive a large number of drugs to treat a multitude of intercurrent conditions. Because of the impaired renal function in ESRD patients, dosage reduction is often recommended to avoid adverse drug reactions, particularly for drugs and active metabolites with extensive renal excretion. On the other hand, if the removal of a drug by haemodialysis during concomitant drug therapy is significant, a dosage supplement would be required to ensure adequate therapeutic efficacy. Knowledge of the impact of haemodialysis on the elimination of specific drugs is therefore essential to the rational design of the dosage regimen in patients undergoing haemodialysis. This review addresses the clinical pharmacokinetic aspects of drug therapy in haemodialysis patients and considers: (a) the effects of ESRD on the general pharmacokinetics of drugs; (b) dialysis clearance and its impact on drug and metabolite elimination; (c) the definition of dialysability and the criteria for evaluation of drug dialysability; (d) pharmacokinetic parameters which are useful in the prediction of drug dialysability; and (e) the application of pharmacokinetic principles to the adjustment of dosage regimens in haemodialysis patients. Finally, drugs commonly associated with haemodialysis therapy are tabulated with updated pharmacokinetics and dialysability information.

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The assessment of fractional drug removal by extracorporeal dialysis

Cited by 14 publications

References 14 publications

Pharmacokinetics of cefmenoxime in patients with impaired renal function and in those undergoing hemodialysis

Pharmacokinetics of cefmenoxime in patients with impaired renal function and in those undergoing hemodialysis

Removal of imipenem and cilastatin by hemodialysis in patients with end-stage renal failure

Drug Therapy in Patients Undergoing Haemodialysis

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