Cimetidine inhibits theophylline clearance in patients with chronic obstructive pulmonary disease: a study using stable isotope methodology during multiple oral dose administration.

Abstract

1 The effect of concurrent cimetidine administration on the disposition of theophylline was investigated in eight male patients (56‐78 years) with chronic obstructive pulmonary disease (COPD). 2 The patients, who were taking oral theophylline preparations chronically (384‐1020 mg/day), received a [15N], [13C]‐labelled analogue of theophylline (10 mg i.v.) before and during cimetidine treatment (1200 mg/day p.o.). 3 During cimetidine treatment trough levels of theophylline increased 34% (6.4 +/‐ 0.8 to 8.6 +/‐ 1.0 micrograms/ml, P less than 0.05), half‐life increased 48% (6.5 +/‐ 0.6 to 9.6 +/‐ 0.8 h, P less than 0.001), and total plasma clearance decreased 33% (3.88 +/‐ 0.46 to 2.59 +/‐ 0.33 l/h, P less than 0.001), without a significant change in volume of distribution or protein binding. 4 The effect of cimetidine on plasma levels of theophylline was maximal within 72 h. Levels returned to control values within 48 h after its discontinuation. 5 Although there was no correlation with mean plasma concentrations of cimetidine, the change in clearance of theophylline correlated with initial clearance values (r = 0.72). 6 Cimetidine reduced the plasma clearance of theophylline in patients with COPD to an extent similar to that reported in healthy volunteers.

Factors affecting the response to inhibition of drug metabolism by cimetidine‐dose response and sensitivity of elderly and induced subjects.

“…Thus while cimetidine can rapidly reverse the effects of rifampicin (Table 2) on antipyrine clearance it should be noted that the enzyme induction is still in evidence after cessation of cimetidine therapy in these subjects. It has also previously been shown both in animals (Speeg et al, 1982) and in man (Patwardhan et al, 1981;Vestal et al, 1983) that the effects of cimetidine on oxidative metabolism dissipate rapidly (within 24 to 48 h) following cessation of therapy and that tolerance does not occur during chronic therapy (Patwardhan et al, 1981). Klotz & Reimann (1980) reported that cimetidine, last dose given 30 min before diazepam, impaired the elimination of diazepam throughout the sampling period (96 h).…”

Individual and combined effects of cimetidine and ciprofloxacin on theophylline metabolism in male nonsmokers.

“…In particular, the inhibitory action of ciprofloxacin during the second treatment period of the study might have been influenced by a residual effect of cimetidine from the first treatment period. Since it takes only 48 h for plasma concentrations of theophylline to return to baseline after discontinuation of cimetidine [13], the 5 day treatment period was sufficiently long for the individual inhibitory effect of cimetidine to disappear prior to the measurement of theophylline kinetics on the fifth day of oral ciprofloxacin administration. Also, the individual inhibitory effects of cimetidine and ciprofloxacin in this study were similar to those reported previously [10,[12][13][14][15][16][17].…”

“…The total volume of the urine samples was measured, and aliquots were stored at -20°C until analysis. Beginning on day 4, each subject received the following: (1) cimetidine 400 mg orally every 12 h for 7 days (study days 4-10), (2) ciprofloxacin 500 mg orally every 12 h for 7 days (study days [11][12][13][14][15][16][17], and (3) cimetidine 400 mg every 12 h and ciprofloxacin 500 mg orally every 12 h for 7 days (study days 18-24). Single-dose pharmacokinetic studies of theophylline were repeated on the fith day of each treatment regimen (study days 8, 15, and 22).…”

UDP-glucose pyrophosphorylase influences polysaccharide synthesis, cell wall components, and hyphal branching in Ganoderma lucidum via regulation of the balance between glucose-1-phosphate and UDP-glucose

“…UDP-Glc, the product/substrate of UGP, is the precursor for the synthesis of different surface structures, lipopolysaccharides (LPS) and extracellular polysaccharides (EPS). UDP-Glc can also be converted to other nucleoside diphosphate sugars that are used in the syntheses of pectic substances, hemicelluloses, glycolipids, and other assorted glycosylated molecules (Vestal et al, 1983). In plants, UDP-Glc can be used as a substrate for disaccharides, such as sucrose and trehalose (Kleczkowski et al, 2004).…”