Dosing implications of altered gentamicin disposition in patients with cystic fibrosis. 1982

G L Kearns, and B C Hilman, and J T Wilson

A pharmacokinetic approach was used for gentamicin dosing in 19 children and young adults with cystic fibrosis. A one-compartment open-model analysis of steady-state gentamicin pharmacokinetics revealed a significantly larger apparent volume of distribution and total plasma clearance for patients with CF as compared to a similar population of children without the disease. The increase in the apparent volume of distribution for patients with CF produced a larger daily gentamicin dose requirement to maintain similar steady-state levels as compared to children without the disease. Significant differences in the elimination rate constant and half-life for gentamicin were not found between these populations. Linear correlations between creatinine clearance and kel for gentamicin, and total body body weight and the apparent volume of distribution were demonstrated for children with varying degrees of stable renal function but not patients with CF. Altered gentamicin disposition peculiar to CF precludes application of currently used dosing nomograms or guidelines derived from normal populations, and emphasizes the need for individualized gentamicin therapy guided by a pharmacokinetic approach in these patients.

UI MeSH Term Description Entries
D007668 Kidney Body organ that filters blood for the secretion of URINE and that regulates ion concentrations. Kidneys
D008171 Lung Diseases Pathological processes involving any part of the LUNG. Pulmonary Diseases,Disease, Pulmonary,Diseases, Pulmonary,Pulmonary Disease,Disease, Lung,Diseases, Lung,Lung Disease
D008657 Metabolic Clearance Rate Volume of biological fluid completely cleared of drug metabolites as measured in unit time. Elimination occurs as a result of metabolic processes in the kidney, liver, saliva, sweat, intestine, heart, brain, or other site. Total Body Clearance Rate,Clearance Rate, Metabolic,Clearance Rates, Metabolic,Metabolic Clearance Rates,Rate, Metabolic Clearance,Rates, Metabolic Clearance
D001830 Body Surface Area The two dimensional measure of the outer layer of the body. Area, Body Surface,Areas, Body Surface,Body Surface Areas,Surface Area, Body,Surface Areas, Body
D001835 Body Weight The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms. Body Weights,Weight, Body,Weights, Body
D002648 Child A person 6 to 12 years of age. An individual 2 to 5 years old is CHILD, PRESCHOOL. Children
D002675 Child, Preschool A child between the ages of 2 and 5. Children, Preschool,Preschool Child,Preschool Children
D002986 Clinical Trials as Topic Works about pre-planned studies of the safety, efficacy, or optimum dosage schedule (if appropriate) of one or more diagnostic, therapeutic, or prophylactic drugs, devices, or techniques selected according to predetermined criteria of eligibility and observed for predefined evidence of favorable and unfavorable effects. This concept includes clinical trials conducted both in the U.S. and in other countries. Clinical Trial as Topic
D003404 Creatinine Creatinine Sulfate Salt,Krebiozen,Salt, Creatinine Sulfate,Sulfate Salt, Creatinine
D003550 Cystic Fibrosis An autosomal recessive genetic disease of the EXOCRINE GLANDS. It is caused by mutations in the gene encoding the CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR expressed in several organs including the LUNG, the PANCREAS, the BILIARY SYSTEM, and the SWEAT GLANDS. Cystic fibrosis is characterized by epithelial secretory dysfunction associated with ductal obstruction resulting in AIRWAY OBSTRUCTION; chronic RESPIRATORY INFECTIONS; PANCREATIC INSUFFICIENCY; maldigestion; salt depletion; and HEAT PROSTRATION. Mucoviscidosis,Cystic Fibrosis of Pancreas,Fibrocystic Disease of Pancreas,Pancreatic Cystic Fibrosis,Pulmonary Cystic Fibrosis,Cystic Fibrosis, Pancreatic,Cystic Fibrosis, Pulmonary,Fibrosis, Cystic,Pancreas Fibrocystic Disease,Pancreas Fibrocystic Diseases

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