The pharmacokinetics of theophylline and enprofylline in patients with liver cirrhosis and in patients with chronic renal disease

Abstract

We have studied the pharmacokinetics of theophylline and enprofylline in patients with liver cirrhosis, patients with chronic renal failure, and healthy subjects, and have assessed the predictive value of routine tests of liver function and renal function (creatinine clearance) for theophylline and enprofylline total body clearances. Theophylline clearance was significantly decreased in the patients with liver cirrhosis compared with both the patients with renal failure and the healthy subjects (the mean values in the three groups were 24, 47, and 46 ml.h-1.kg-1 respectively. Enprofylline clearance was significantly decreased in the patients with chronic renal failure, compared with both the patients with liver cirrhosis and the healthy subjects (the values in the three groups were 64, 250, and 289 ml.h-1.kg-1 respectively. There was a strong correlation between creatinine clearance and enprofylline clearance, while there was only a poor correlation between the liver function tests and theophylline clearance. It appears that in various clinical situations enprofylline elimination can be predicted more precisely than theophylline elimination, which may make the drug safer in clinical practice.

A prospective clinical study of theophylline safety in 3810 elderly with asthma or COPD

“…This result is consistent with the reports that theophylline clearance decreases due to hepatic disease. [14][15][16][17][18] In conclusion, low-dose sustained-release theophylline can be used with acceptable safety in most elderly patients with asthma and COPD.…”

“…Most serious adverse events of theophylline have been observed when the drug was overdosed. 5 However, adverse events of theophylline may develop also in patients who are taking the usual dose because the clearance of theophylline is modified by various factors, including aging, [6][7][8][9][10][11][12][13] a reduction in physiological hepatic function [14][15][16][17][18][19][20] and drug interactions with other medications. 21,22 To investigate the incidence and severity of such adverse events, we studied elderly patients who received sustainedrelease theophylline in the present large-scale prospective study.…”

The pharmacokinetics of γ‐glutamyl‐l‐dopa in normal and anephric rats and rats with glycerol‐induced acute renal failure

“…Thus it is of interest to know what effect renal failure has on the disposition of gludopa. Studies on the influence of renal failure on the disposition of drugs have mainly concentrated on effects on hepatic drug metabolising enzymes (Van Peer & Belpaire, 1977;Leber et al, 1978;Patterson & Cohn, 1984) and on the problems associated with drugs excreted mostly unchanged by the kidneys (Jackson et al, 1988;Kraan et al, 1988;Williams et al, 1988). Little is known about the effect of uraemia on the disposition of drugs metabolised mostly by the kidney.…”

Liver dysfunction markedly decreases the inhibition of cytochrome P450 1A2–mediated theophylline metabolism by fluvoxamine

“…Although various studies have shown that theophylline disposition is greatly impaired in liver cirrhosis, 21 , 22 , 28 , 29 , 30 , 31 only the study by Staib et al 22 investigated the effect of cirrhosis on the individual metabolic pathways of theophylline. These authors, who measured 24‐hour urinary recoveries, found increased urinary excretion of 1‐MU and decreased excretion of 3‐MX.…”