Lithium pharmacokinetics in the obese

Reiss, R A; Haas, Curtis E.; Karki, Shyam D; Gumbiner, Barry M.; Welle, Stephen; Carson, Stanley W.

doi:10.1038/clpt.1994.47

Cited by 45 publications

(20 citation statements)

References 2 publications

(2 reference statements)

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“…In a study in obese patients [33] a greater clearance compared to normal weight adults which correlated with total body weight but not creatinine clearance was reported. Volume of distribution correlated with fat-free mass, but volume per kg total body weight was lower in obese compared to normal weight subjects.…”

Section: Discussionmentioning

confidence: 99%

First-Dose Pharmacokinetics of Lithium Carbonate in Children and Adolescents

Findling

Landersdorfer

Kafantaris

et al. 2010

Journal of Clinical Psychopharmacology

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This study examines the pharmacokinetics of oral doses of lithium carbonate immediate-release capsules after administration of 600 or 900 mg in children and adolescents with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, bipolar I disorder. Lithium plasma concentrations were followed over 48 to 72 hours in 39 subjects (20 male and 19 female subjects; ages, 7-17 years) with mixed or manic episodes enrolled at 7 clinical sites participating in the Collaborative Lithium Trials. Population pharmacokinetic modeling was performed using NONMEM, and influences of patient covariates on pharmacokinetics parameters were examined. The pharmacokinetics of lithium was best described using a 2-compartment model with a lag time and first-order absorption. There was considerable variability in lithium exposures. Lithium clearance related best to fat-free mass. Inclusion of fat-free mass as a covariate reduced the between-subject variability from 52% to 42%. Lithium clearances did not vary systematically with age group, dose, sex, or creatinine clearances. Allometrically scaled clearance and volume of distribution from the population analysis were within the range reported in adults. Single-dose profiles of lithium in young patients with BP-1 show marked variability. Therefore, ongoing serum monitoring is needed during continued therapy. The developed population pharmacokinetic model may be used to predict other dosage regimens, support scaling from adult to pediatric pharmacokinetics, and support the design of future clinical trials.

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Section: Discussionmentioning

confidence: 99%

First-Dose Pharmacokinetics of Lithium Carbonate in Children and Adolescents

Findling

Landersdorfer

Kafantaris

et al. 2010

Journal of Clinical Psychopharmacology

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“…There are several discrepancies regarding the influence of obesity on these functions. While some studies have shown an increase in glomerular filtration, measured using creatinine clearance, in obese women as compared to normal weight women [19][20][21], others have shown decreased glomerular filtration [22] or no significant difference between creatinine clearance in obese versus non-obese individuals [23,24]. These discrepancies might be due to the difference in extent of obesity and/or associated renal pathology.…”

Section: Discussionmentioning

confidence: 99%

Carboplatin dosing in overweight and obese patients with normal renal function, does weight matter?

Ekhart

Rodenhuis

Schellens

et al. 2008

Cancer Chemother Pharmacol

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Purpose The purpose of this study was to determine the potential utility of alternative weight descriptors in the Cockcroft-Gault equation to more accurately predict carboplatin clearance in underweight, normal weight, overweight and obese patients.Methods Clearance values obtained from individual fits using NONMEM were compared to predicted carboplatin clearances calculated using the modified Calvert formula in which creatinine clearance was calculated with the Cockcroft-Gault equation using diverse weight descriptors. Results This study indicated that lean body mass was the best weight descriptor in underweight and normal weight patients, while adjusted ideal body weight was the best weight descriptor in overweight and obese patients. However, a flat dose based on the population carboplatin clearance performed better in all weight categories than the use of the Cockcroft-Gault equation with diverse weight descriptors. Conclusion These results suggest that in overweight and obese patients, with a normal renal function, a flat carboplatin dose should be administered, based on the population carboplatin clearance (8.38 l/h = 140 mL/min). Thus, in case an AUC of 5 mg min/mL is desired, the appropriate dose for carboplatin would be 5 9 140 = 700 mg.

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“…Dionne et al 64 has also shown increased creatinine clearance in obese subjects when compared to historical values of creatinine clearance; however, Ducharme et al 65 showed decreased glomerular filtration via creatinine clearance in obese individuals from a patient population study of vancomycin pharmacokinetics. Reiss et al 66 and Allard et al 67 showed no significant difference between creatinine clearance in obese versus nonobese individuals. There are also discrepancies between studies of drug primarily excreted by glomerular filtration.…”

Section: Changes In Renal Function In Obese Humansmentioning

confidence: 97%

“…Changes in tubular function have been indicated in several studies. The renal clearance of ciprofloxacin, 67 cimetidine, 72,73 procainamide, 32,45 and lithium 66 has been shown to increase in obese individuals. Since the renal excretion of ciprofloxacin, 92 cimetidine, 95 and procainamide 32 involves primarily glomerular filtration and tubular secretion, the increases in renal clearance of ciprofloxacin, cimetidine, and procainamide accompanied by a disproportionate increase in glomerular filtration supports increased tubular secretion in obese individuals.…”

Section: Changes In Renal Function In Obese Humansmentioning

confidence: 98%