Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of hepatic disease on the pharmacokinetics of the histamine H2-receptor antagonist famotidine were studied in seven healthy volunteers and 20 patients with chronic liver disease. The acute effects of famotidine on hepatic hemodynamics were studied in six healthy volunteers and eight patients with chronic liver disease, and its long-term effects on peptic ulcer, portal blood flow, and hepatic function were studied in 34 patients with chronic liver disease and peptic ulcer. Famotidine clearance was reduced only in patients with decompensated cirrhosis, probably because of concomitant renal impairment. Infusion of 20 mg of famotidine did not reduce hepatic or portal blood flow in healthy subjects, nor did it reduce the gradient between wedged hepatic vein pressure and free hepatic vein pressure or hepatic and portal blood flow in patients with chronic liver disease. An oral dose of 20 mg of famotidine twice daily for two months healed the peptic ulcers in 33 of 34 patients (97%) with chronic liver disease without altering portal blood flow and hepatic function. Even in patients with decompensated cirrhosis, famotidine did not change hepatic function. Thus, famotidine had no effect on hepatic hemodynamics or function in healthy subjects and patients with chronic liver disease. The drug was shown to be well tolerated and effective in the treatment of gastric and duodenal ulcer associated with chronic liver disease.
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PMID:Effects of hepatic disease on the pharmacokinetics of famotidine and effects of famotidine on hepatic hemodynamics and peptic ulcer. 221 Jun 13

Three different studies were conducted to assess the pharmacokinetics of moclobemide in subjects with conditions complicating dose determination. The first examined the absorption and disposition of moclobemide in an elderly population and compared these with results obtained in a group of normal young subjects. No significant differences were found between the groups in the intravenous (i.v.) parameters of disposition, and no differences with regard to disposition of the metabolite, Ro 12-8095. In addition, the minimum steady-state concentrations of moclobemide and the main plasma metabolite did not differ between the elderly and younger patients. In the second study, clearance tests in patients with cirrhosis of the liver confirmed that hepatic function is drastically reduced in this group of patients; it is therefore possible that moclobemide absorption and distribution might be influenced. In only 3 of the 12 patients investigated, slowly declining plasma concentrations after administration pointed to a severely limited elimination capacity for moclobemide. In the remaining 9 subjects, average values of several parameters changed significantly (t 1/2 beta, MRT and C1), whereas Vss and renal clearance were not significantly altered. In patients with kidney dysfunction, there were no differences in kinetics between patients undergoing hemodialysis and those who were not. Compared with normal healthy volunteers, no differences were found for renal patients, with the exception of the mean absorption time, which was significantly prolonged. From these studies it can be concluded that, pharmacokinetically, neither age nor renal impairment require adjusting the dosage of moclobemide. Patients with liver cirrhosis, however, need to have the usual dose reduced to one half or one third, or else the dosage intervals can be increased to prevent cumulation.
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PMID:Absorption and disposition of moclobemide in patients with advanced age or reduced liver or kidney function. 224 88

Repeated large-volume paracentesis (4-6 L/day) is an effective and safe therapy of ascites in patients with cirrhosis provided albumin is infused intravenously. To investigate whether ascites can be safely mobilized in only one paracentesis session ("total paracentesis"), 38 cirrhotic patients with tense ascites were treated with total paracentesis plus intravenous albumin (6-8 g/L ascites removed). Standard liver tests and renal function tests, glomerular filtration rate, free water clearance, plasma volume, plasma renin activity, and plasma aldosterone and norepinephrine concentrations were measured before and after treatment. Total paracentesis was effective in mobilizing ascites in all but 1 patient and did not impair any of the parameters studied. The volume of ascitic fluid removed and the duration of the procedure were 10.7 +/- 0.5 L (mean +/- SEM) and 60 +/- 3 min, respectively. Five of the 38 patients (13%) developed complications during the first hospital stay (hepatic encephalopathy and gastrointestinal hemorrhage in 2 patients each and culture-negative bacterial peritonitis in 1). No patient developed renal impairment. This complication rate, as well as the clinical course of the disease during follow-up, estimated by the probability of readmission to hospital, causes of readmission, and survival probability after treatment, was similar to that reported in patients treated with repeated large-volume paracentesis. These results indicate that total paracentesis associated with intravenous albumin can be safely performed in cirrhotic patients with tense ascites and suggest that these patients could be treated in a single-day hospitalization regime.
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PMID:Total paracentesis associated with intravenous albumin management of patients with cirrhosis and ascites. 229 73

Nonsteroidal antiinflammatory drugs (NSAID), such as indomethacin, reduce production of renal prostaglandins and markedly impair renal function in patients with cirrhosis and ascites. To determine if simultaneous administration of oral prostaglandin analogs minimizes the renal impairment, 10 patients received indomethacin and either misoprostol or placebo in a double-blind, crossover study. Indomethacin reduced urinary sodium from 23 +/- 9 to 8 +/- 4 microEq/min in 4 hours. Misoprostol with indomethacin tended to prevent the fall in urinary sodium (from 35 +/- 15 to 46 +/- 21 microEq/min at 4 hours), but sodium excretion fell to the same level in both groups by 8 hours (6 +/- 3 microEq/min). Indomethacin reduced creatinine clearance in 4 hours by 49%; misoprostol plus indomethacin reduced creatinine clearance by only 34%. Misoprostol tended to minimize or delay the nephrotoxic effects of indomethacin, suggesting that more potent prostaglandin analogs may prevent the renal impairment induced by NSAID.
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PMID:Effects of oral prostaglandins on indomethacin-induced renal failure in patients with cirrhosis and ascites. 232 52

The pharmacokinetics of etodolac, a new nonsteroidal anti-inflammatory drug, were compared in normal subjects, in patients with renal and hepatic disease, and in elderly patients. In 28 normal subjects, orally administered etodolac was rapidly absorbed. By 1.2 hours after ingestion of a 200 mg dose, the maximum serum concentration (Cmax) averaged 15.9 micrograms/ml, with more than 99% of the drug bound to serum protein. Clearance was primarily hepatic. The mean half-life (t1/2) was 6 to 7 hours. There were no apparent differences in Cmax, the time at which Cmax occurred (tmax), area under the serum concentration/time curve (AUC0-24), or t1/2 between groups of young men (n = 20), elderly men (n = 24), and elderly men with osteoarthritis (n = 20), after a single dose of etodolac or after 7 days of subchronic administration. Moreover there was no evidence of accumulation. There also were no differences in Cmax, tmax, AUC0-24 or t1/2 between groups of normal subjects (n = 10) and patients with mild-to-moderate renal impairment (n = 10). Patients with end-stage renal disease who were receiving chronic hemodialysis had the same mean serum concentration of free drug as normal subjects, even though mean serum levels of protein-bound etodolac were slightly lower than those in the normal subjects. The only significant (p less than 0.05) difference between patients with stable hepatic cirrhosis and normal, age-matched subjects was a slightly shorter tmax in the cirrhotic subjects (1.1 vs. 1.4 hours). These findings suggest that no alteration of etodolac dosage would be necessary in these high-risk groups.
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PMID:Profile of etodolac: pharmacokinetic evaluation in special populations. 252 81

Bacterial infection is a serious and often fatal complication of patients with liver disease and can prove fatal either directly or by precipitation of gastrointestinal bleeding, renal failure, or hepatic encephalopathy. At greatest risk are patients with alcoholic cirrhosis or decompensated chronic liver disease, or cases of acute liver disease who progress to fulminant hepatic failure or subacute hepatic necrosis. Infection appears to be unusual in patients with primary biliary cirrhosis. The site and type of infection is unrelated to the aetiology of the liver disease. Bacteraemia, pneumonia, urinary tract infection and spontaneous bacterial peritonitis are most common but infective endocarditis and meningitis, especially with pneumococci, are easily overlooked. Clinical suspicion of infection must be high as the only indication may be a general deterioration in the patients' clinical state, increasing encephalopathy or renal impairment. In the case of patients with fulminant hepatic failure, infection may precipitate the initial or recurrent encephalopathy and contributes to death in 10% of fatal cases. Spontaneous bacterial peritonitis is now recognized to occur in the absence of clinical features of peritonitis. The PMN content of the ascitic fluid may provide the only indication of infection and is the most readily available screening test. The most common types of organism responsible for all types of infection are Gram-negative enteric and streptococci, especially pneumococci, while infection with anaerobes is rare. Risk factors for infection include decompensated alcoholic liver disease, fulminant hepatic failure, gastrointestinal bleeding, invasive practical procedures and impaired host defence mechanisms against infection. Of the host defence mechanisms, impaired function of the reticuloendothelial system, complement, and PMNs represent the most common and serious defects. Defects of humoral immunity are present in ascitic fluid from patients with cirrhosis and are probably a major reason for development of spontaneous bacterial peritonitis. Diuresis improves these functions and reduces the risk of peritonitis. Treatment of infections even with the appropriate antibiotic is still associated with a high mortality but the use of adjuvant gut sterilization is promising, particularly in cases infected with Gram-negative enteric organisms. Infusions of fresh frozen plasma, blood and cryoprecipitate improve some systemic host defences and may be beneficial in the treatment and reduction of risk of infection.
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PMID:Bacterial infections complicating liver disease. 265 49

The effect of encainide administration on steady-state plasma digoxin levels was evaluated in 17 patients receiving stable doses of digoxin. A paired t test, comparing plasma digoxin levels (mean +/- standard error) before encainide therapy (1.05 +/- 0.14 ng/ml) and after 2 weeks of encainide, 100 mg/day (1.03 +/- 0.11 ng/ml) or 200 mg/day (1.2 +/- 0.2 ng/ml), indicates no significant (p greater than 0.05) change in digoxin levels. These results were confirmed in a second study of 10 patients with severe congestive heart failure. Also, no difference in efficacy of either drug was observed and changes in dosing of digoxin were not required. Plasma concentrations of encainide and its 2 major metabolites, O-demethyl encainide (ODE) and 3-methoxy-O-demethyl encainide, significantly increased by 31.6%, 43.1% and 35.6% after concomitant cimetidine administration in 13 healthy adult men receiving 75 mg/day of encainide. However, a retrospective evaluation of 33 patients receiving both drugs did not reveal any clinically significant interactions. Retrospective evaluation of patients enrolled in clinical studies who received concomitant digoxin (268), antiarrhythmics (118), anticoagulants (78), antidiabetics (40), antipsychotics (23), beta blockers (88), calcium-channel blockers (24) or diuretics (229) did not reveal any clinically significant interactions with encainide. Similarly, in vitro protein binding studies did not reveal any clinically significant interactions with encainide or its major metabolites. Six patients with moderate to severe renal impairment (creatinine clearance 10 to 38 ml/min) received 25 mg of encainide, 3 times/day, for 7 doses. Plasma encainide, ODE and 3-methoxy-O-demethyl concentrations were similar to those observed in normal subjects who had received twice the dose of encainide, and steady-state apparent oral clearance of encainide was reduced by 66% with renal impairment. Based on these data it is recommended that in patients with moderate to severe renal impairment encainide be initiated at one-third the normal dose, or 25 mg once a day. Doses may be elevated in small increments at 1-week intervals if needed for efficacy. The effect of hepatic impairment on the pharmacokinetics of encainide was studied in 7 patients with clinically documented cirrhosis. Compared with normal subjects studied using a similar protocol, the plasma concentrations of encainide were elevated significantly due to a 6-fold decrease in oral clearance. However, since plasma concentrations of the active metabolite ODE were correspondingly lower, specific encainide dosing instructions for patients with hepatic impairment are not indicated.
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PMID:Drug interaction studies and encainide use in renal and hepatic impairment. 287 43

The pharmacokinetics of bisoprolol were investigated following oral administration of 10mg once daily for 7 days in 8 healthy subjects, in 14 patients with different degrees of renal impairment and in 18 patients with liver disease. In healthy subjects peak and trough steady-state concentrations of 52 micrograms/L and 11 micrograms/L, respectively, an elimination half-life of 10.0 hours and total body clearance of 14.2 L/h were observed. 5.21 mg/24 hours of unchanged bisoprolol were recovered following urinary excretion during the dosage interval. In 11 patients with renal impairment (mean CLCR = 28 +/- 5 ml/min/1.72m2) half-life was prolonged to 18.5 hours, and peak and trough concentrations were 74 and 32 micrograms/L, respectively. Correspondingly, urinary excretion decreased to 3.35 mg/24 hours and total body clearance to 7.8 L/h. In uraemic patients (CLCR less than 5 ml/min/1.73m2) the total clearance of bisoprolol was 5.0 L/h and the elimination half-life was 24.2 hours. In patients with liver cirrhosis half-life increased to 13.5 hours, steady-state peak and trough concentrations increased to 62 and 22 micrograms/L, respectively, and total body clearance decreased to 10.8 L/h. The present study indicates that in patients with impairment of kidney or liver function accumulation of bisoprolol above a factor of 2 did not occur. However, in the terminal stages of insufficiency of kidney or liver function bisoprolol dosage should not exceed 10mg.
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PMID:Pharmacokinetics of bisoprolol during repeated oral administration to healthy volunteers and patients with kidney or liver disease. 288 25

The pharmacokinetics of ibopamine was studied after single dose and after single and multiple dosing. The studies after single dose were conducted in normal subjects (NS) and in patients with congestive heart failure (CHF) of NYHA functional classes II, III and IV, in patients with chronic renal impairment (CRI), with hepatic cirrhosis (HC) and in elderly patients. Furthermore, ibopamine-quinidine pharmacokinetic interaction and the effects of food on plasma kinetics were evaluated in NS. The studies after single and multiple dosing were conducted in CHF patients. The effects were also studied of chronic oral ibopamine treatment on the pharmacokinetics of digoxin after chronic oral dosing and of treatment with digoxin on ibopamine pharmacokinetics. Ibopamine appears to be rapidly and extensively absorbed, quickly hydrolyzed to epinine and then excreted mainly through the kidneys either after being sulpho-conjugated or oxidized to homovanillic acid and 3,4-dihydroxyphenylacetic acid. Epinine is thought to be the therapeutically active moiety of the drug. In patients with CHF epinine pharmacokinetics does not depend on the NYHA functional class, and it falls within the same area as that in NS; the pharmacokinetics of epinine does not vary during the repeated administration of the drug for one month. In patients with CHF the pharmacokinetic data do not suggest the need to adjust the dose according to the NYHA functional class. In patients with CRI the pharmacokinetics of epinine does not vary with the degree of renal impairment. In HC patients AUC and Cmax of epinine seem to be higher than in NS; in these patients a higher amount of epinine is excreted into urine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical pharmacokinetics of ibopamine on different diseases and conditions. 290 70

Nonsteroidal anti-inflammatory drugs such as indomethacin induce a rapid reduction in renal perfusion and blunt the effects of diuretics in patients with cirrhosis and ascites. Nonacetylated salicylates reportedly cause less reduction in renal prostaglandins than do aspirin and other nonsteroidal anti-inflammatory drugs. To determine whether nonacetylated salicylates affect renal function, we compared diflunisal with indomethacin in nine patients with cirrhosis and ascites. One 50-mg dose of indomethacin reduced inulin clearance (91 +/- 11 to 76 +/- 11 ml/min) and blunted furosemide-stimulated natriuresis (58 +/- 12 to 36 +/- 9 mEq/h) and diuresis (1103 +/- 148 to 809 +/- 170 ml/h, all p less than 0.05). Three doses of diflunisal had no effect on inulin clearance (94 +/- 16 ml/min), natriuresis (60 +/- 12 ml/h), or diuresis (1041 +/- 112). Indomethacin caused greater reduction in urinary prostaglandin E2 (50% vs. 10%) and in serum thromboxane (94% vs. 80%) than diflunisal (p less than 0.05). Thus, nonacetylated salicylates avoid renal impairment and may be the preferred nonsteroidal anti-inflammatory drug in patients with cirrhosis and ascites.
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PMID:Comparative acute effects of diflunisal and indomethacin on renal function in patients with cirrhosis and ascites. 291 25


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