Chronic pulmonary disease and antipyrine disposition.

Agnihotri, S. K.; Clark, R D; Cooper, Stephen A.; Iyun, AO; Tucker, GT

doi:10.1111/j.1365-2125.1978.tb01641.x

Cited by 12 publications

(2 citation statements)

References 9 publications

(8 reference statements)

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“…Support for this assertion, however, has been provided almost exclusively by studies (both pharmacokinetic and phenotyping) in adults with CF. Given the known effects of growth and development and disease pathophysiologic characteristics 39 , 40 , 41 and severity 12 , 42 on hepatic biotransformation, it is difficult to extrapolate information from adult to pediatric CF populations. The systematic assessment of the activity of hepatic drug‐metabolizing enzymes in children with CF is, therefore, essential.…”

Section: Discussionmentioning

confidence: 99%

Activities of Cytochrome P450 1A2, N‐acetyltransferase 2, Xanthine oxidase, and Cytochrome P450 2D6 are Unaltered in Children with Cystic Fibrosis

Kennedy

Scripture

Kashuba

et al. 2004

Clin Pharma and Therapeutics

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The activities of hepatic cytochrome P450 (CYP) 1A2, N-acetyltransferase 2 (NAT-2), xanthine oxidase (XO), and CYP2D6 were evaluated in 12 young children (aged 3-8 years) with mild cystic fibrosis (CF) and 12 age-matched healthy control subjects by use of standard caffeine and dextromethorphan phenotyping methods. Subjects were given 4 oz of Coca-Cola (approximately 35 mg caffeine) (The Coca-Cola Company, Atlanta, Ga) and a single 0.5-mg/kg dose of dextromethorphan. Urine was collected for 8 hours after biomarker administration, and enzyme activity was assessed by use of previously validated caffeine and dextromethorphan molar ratios. CYP2D6 genotyping was also performed in 10 of 12 subjects with CF and 11 of 12 control subjects. There were no significant differences in the urinary molar ratios for any of the enzyme systems evaluated. These data suggest that CF does not alter the activities of CYP1A2, NAT-2, XO, and CYP2D6. Altered biotransformation of drugs in this patient population is likely enzyme- and isoform-specific and thus is apparent for only selected compounds that are substrates for enzymes other than CYP1A2, NAT-2, XO, and CYP2D6.

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Section: Discussionmentioning

confidence: 99%

Activities of Cytochrome P450 1A2, N‐acetyltransferase 2, Xanthine oxidase, and Cytochrome P450 2D6 are Unaltered in Children with Cystic Fibrosis

Kennedy

Scripture

Kashuba

et al. 2004

Clin Pharma and Therapeutics

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“…A 30 % decrease in apparent volume of distribution of antipyrine was reported in a group of 8 patients with chronic hypoxia (P a 0 2 = 51 ± 10mm Hg. mean ± SD) secondary to chronic obstructive pulmonary disease (COPD) in 6 subjects and I or pulmonary fibrosis in 2 others (Agnihotri et al, 1978). These changes persisted after correction of hypoxia for 24 hours.…”

Section: Drug Distributionmentioning

confidence: 92%

Pulmonary Disease and Drug Kinetics

Souich

McLean

Lalka

et al. 1978

Clinical Pharmacokinetics

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A number of examples of altered drug disposition in patients with respiratory disease have been reported. These reports have been analysed in terms of absorption, distribution and elimination. The changes have been examined mechanistically in light of the pathophysiology of respiratory disease and the known influence of these physiological parameters on drug disposition. Our analysis has included in vivo and in vitro data from laboratory animals in addition to appropriate data from humans.Acute hypoxaemia appears to decrease intrinsic hepatic clearance while chronic hypoxia appears to increase intrinsic clearance. The free fraction of some bases is decreased in plasma taken from patients with chronic hypoxaemia and this change can interact with changes in intrinsic metabolic activity. Blood gas disturbances also can affect drug disposition by decreasing hepatic and renal perfusion. Cor pulmonale has not been linked to altered drug disposition, except in the case of theophylline. However, this pathophysiological condition may be equivalent to congestive cardiac failure through diminished hepatic and renal perfusion.The marked reduction (approximately 50 %) in theophylline clearance documented in some asthmatic patients may reflect protein binding changes, a paradoxical response of metabolic pathways to hypoxaemia, or other as yet unidentified processes ..It is apparent that respiratory disease significantly changes drug disposition through a number of interacting mechanisms. These have not been adequately studied to provide a basis for clinical dosage adjustment, however, general principles are emerging: Drugs showing flowdependent hepatic clearance (e.g. lignocaine/lidocaine, pethidine/meperidine, propoxyphene) and those drugs showing predominant renal clearance (aminoglycosides, digoxin) should be used with caution. Theophylline doses must be reduced on an empirical basis, as the mechanisms causing reduced clearance cannot be convincingly explained in terms of the pathophysiology of respiratory disease.The lungs must be added to the existing list of organs (liver, kidney, heart) whose dysfunction significantly affects drug disposition.

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Influence of chronic obstructive lung disease on the disposition of an acidic drug (sulfamethazine)

Souich¹

1983

Archives of Internal Medicine

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The influence of chronic respiratory failure (CRF) on the pharmacokinetics of an acidic drug has been studied in 11 patients and in eight normal volunteers who received 10 mg/kg of oral sulfamethazine. Blood and urine samples were collected for 24 and 48 hours, respectively. No differences were observed in the rate of sulfamethazine absorption, but bioavailability was decreased when compared with control subjects. Sulfamethazine volume of distribution (Vd) was larger in patients than in control subjects. These differences in Vd may be secondary to an increase in sulfamethazine unbound fraction. No differences were observed in sulfamethazine elimination. It is concluded that in patients with CRF sulfamethazine bioavailability decreases, and Vd increases secondary to a decrease in binding. Despite the fact that plasma concentrations of the test drug will be decreased, the administration of higher doses may not be advisable.

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Chronic pulmonary disease and antipyrine disposition.

Cited by 12 publications

References 9 publications

Activities of Cytochrome P450 1A2, N‐acetyltransferase 2, Xanthine oxidase, and Cytochrome P450 2D6 are Unaltered in Children with Cystic Fibrosis

Activities of Cytochrome P450 1A2, N‐acetyltransferase 2, Xanthine oxidase, and Cytochrome P450 2D6 are Unaltered in Children with Cystic Fibrosis

Pulmonary Disease and Drug Kinetics

Influence of chronic obstructive lung disease on the disposition of an acidic drug (sulfamethazine)

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