Impaired elimination of caffeine in cirrhosis

Desmond, Paul; Patwardhan, Rashmi; Johnson, Raymond F.; Schenker, Steven

doi:10.1007/bf01308138

Cited by 75 publications

(47 citation statements)

References 7 publications

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“…Indeed it has been shown that plasma caffeine clearance is significantly reduced in patients with cirrhosis and its elimination half-life is significantly prolonged (Desmond et al, 1980;Wietholtz et al, 1981;Renner et al, 1984;Wang et al, 1985). Although caffeine loading tests are inexpensive, simple to perform and safe, the test procedure has yet to be standardised and there are few guidelines as to how the test results should be interpreted.…”

Section: Introductionmentioning

confidence: 99%

The pharmacokinetics of caffeine and its dimethylxanthine metabolites in patients with chronic liver disease.

Scott

Stambuk

Chakraborty

et al. 1989

Brit J Clinical Pharma

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1. Serum and salivary concentrations of caffeine (1,3,7‐ trimethylxanthine) and its dimethylxanthine metabolites were measured in 10 healthy control subjects and in 19 patients with cirrhosis, for up to 96 h following a 400 mg oral caffeine load. 2. Serum and salivary caffeine concentrations correlated significantly (r = 0.954; P less than 0.001) and no significant differences were observed in the pharmacokinetic data derived from the respective concentration‐time curves. 3. In the control subjects, basal salivary caffeine concentrations did not exceed 0.4 mg l‐1. The median (range) basal salivary caffeine concentrations in patients with compensated cirrhosis (n = 10), 0.2 (0‐0.7) mg l‐1 and decompensated cirrhosis (n = 9), 0.7 (0‐5.8) mg l‐1, were not significantly different from control values, although three patients with decompensated cirrhosis had basal salivary caffeine values above 2.0 mg l‐1. 4. In the patients with compensated cirrhosis, the median peak salivary caffeine concentration, 10.9 (8.2‐ 16.5) mg l‐1 was significantly greater than in controls, 7.1 (4.7‐11.8) mg l‐1 (P less than 0.01) and the median apparent volume of distribution was significantly reduced, 0.38 (0.19‐0.49) vs 0.41 (0.23‐ 0.63) l kg‐1 (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Introductionmentioning

confidence: 99%

The pharmacokinetics of caffeine and its dimethylxanthine metabolites in patients with chronic liver disease.

Scott

Stambuk

Chakraborty

et al. 1989

Brit J Clinical Pharma

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“…This may have resulted in potential delays in absorption of caffeine, particularly in those subjects with cirrhosis. However, it has been shown that the time to peak plasma caffeine concentrations as well as peak caffeine levels after oral administration are not significantly different between cirrhotic and control patients, 4 suggesting that differences in substrate absorption do not significantly contribute to the altered pharmacokinetics of caffeine observed in cirrhosis. This was corroborated by our pharmacokinetic and breath curve data and thus it is reasonable to assume consistent and predictable high oral bioavailability of 13 Ccaffeine in all grades of liver disease.…”

Section: Discussionmentioning

confidence: 99%

“…In calculating the plasma kinetics of caffeine, we limited the collection of caffeine concentrations to 7 hours, despite an observed range of mean caffeine half-lives of 5 (control) to 15 hours (cirrhotic). Notwithstanding the logistical difficulties of a more prolonged collection time and given that the monoexponential decline of plasma caffeine levels is maintained beyond 4 to 5 half-lives, 4 we felt that the collection period of 7 hours was adequate. Moreover, when the data were re-analyzed using the finite area under the concentrationtime curve to the last detectable observation (AUC 0-7 h ) instead of that to infinity, the correlation between plasma and breath caffeine measurements still was maintained (r ϭ 0.74, P Ͻ .001).…”

Section: Discussionmentioning

confidence: 99%

“…4 Serum and salivary caffeine clearance have been shown to be predictive of mortality in cirrhosis 6,7 and salivary caffeine clearance correlates with the more traditional quantitative assays, indocyanine green clearance, galactose elimination capacity, and the aminopyrine breath test. 8 However, significant technical limitations exist in evaluating caffeine kinetics in blood and saliva.…”

mentioning

confidence: 99%

“…1,2 It has high oral bioavailability and undergoes almost exclusive hepatic metabolism, principally via demethylation by cytochrome P450 1A2 (CYP1A2) to CO 2 . 3 It has a low extraction ratio and low plasma binding, 4 and at the test doses used may be considered innocuous. These characteristics render caffeine an ideal substrate for a breath test of hepatic function.…”

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confidence: 99%

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Validity of the 13C–Caffeine Breath Test As A Noninvasive, Quantitative Test of Liver Function

Park

2003

Hepatology

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The properties of caffeine render it an ideal substrate for a quantitative test of liver function. The aim of this study was to determine whether the caffeine breath test (CBT) using orally administered 13 C-caffeine correlates reliably with plasma caffeine clearance and reflects varying degrees of liver dysfunction. The CBT was performed in 25 healthy controls; 20 subjects with noncirrhotic, chronic hepatitis B or C; and 20 subjects with cirrhosis. Plasma caffeine clearance was assayed simultaneously with the CBT in a cohort of these subjects. Over a broad range of caffeine clearances, the CBT exhibited a highly significant correlation with plasma clearance (r ‫؍‬ 0.85, P < .001). Cirrhotic patients were characterized by significantly reduced CBT values (1.15 ؎ 0.75 ‚‰ mg ؊1 ) compared with controls (2.23 ؎ 0.76; P ‫؍‬ .001) and hepatitic patients (1.83 ؎ 1.05; P ‫؍‬ .04). There was a significant inverse relationship between the CBT and Child-Pugh score (r ‫؍‬ ؊.74, P ‫؍‬ .002). The intraclass correlation coefficient between repeated CBTs in 20 subjects with normal and cirrhotic livers was 0.89. Although smoking was associated with an 86% to 141% increase in CBT in all groups, the CBT was able to distinguish control, hepatitic, and cirrhotic smokers (5.36 ؎ 0.82, 3.63 ؎ 1.21, and 2.14 ؎ 1.14, respectively, P ‫؍‬ .001). Multivariate analysis revealed that only smoking (P < .001) and disease state (P ‫؍‬ .001) were significant predictors of the CBT. In conclusion, the 13 C-CBT represents a valid indicator of plasma caffeine clearance and correlates reproducibly with hepatic dysfunction. (HEPATOLOGY 2003;38:1227-1236

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Caffeine: A Model Compound for Measuring Liver Function

et al. 1984

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The effects of liver disease on caffeine plasma clearance (Cl) and on exhalation of 14CO2 following i.v. injection of 2 mu Ci of [3-methyl-14C]caffeine together with 125 mg of the unlabeled compound were measured in 15 patients with cirrhosis, 11 subjects with miscellaneous liver disease, and 10 normal volunteers. Compared to mean values for Cl (2.02 +/- S.D. 0.68 ml per min per kg) and t1/2 (3.8 +/- 0.9 hr) in normal volunteers, cirrhotics were characterized by highly significant reductions in Cl (to 0.76 +/- 0.40) and prolongation in t1/2 (to 13.7 +/- 13.0), whereas the volume of distribution (VD) remained relatively unchanged (0.57 +/- 0.16 vs. 0.64 +/- 0.13 liter per kg in normals). Cumulative 14CO2 production and specific activity of 14CO2 in breath decreased in parallel (r = 0.83) with Cl. Patients with miscellaneous liver disease exhibited only small changes in Cl and t1/2; however, 14CO2 parameters in breath appeared more sensitive in indicating the slight functional derangement. In view of the correlation (Rs = 0.83) of cumulative 14CO2 excretion with the initial disappearance constant for bromosulfophthalein, the caffeine breath test may be considered as a quantitative measure of hepatic microsomal activity; based on a surprisingly close, hyperbolic relationship between Cl and fasting caffeine plasma concentrations, the latter might serve as a simple guide to severity of liver disease.

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Impaired elimination of caffeine in cirrhosis

Cited by 75 publications

References 7 publications

The pharmacokinetics of caffeine and its dimethylxanthine metabolites in patients with chronic liver disease.

The pharmacokinetics of caffeine and its dimethylxanthine metabolites in patients with chronic liver disease.

Validity of the 13C–Caffeine Breath Test As A Noninvasive, Quantitative Test of Liver Function

Caffeine: A Model Compound for Measuring Liver Function

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