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

Salicylamide glucuronide (SAMG) in 0-6 and 6-12 hours-urine specimens was determined after oral administration of salicylamide in 7 normal volunteers (NV), in 51 cases of various liver diseases and hyperbilirubinemias, and in 19 cases after drug administration, to predict the in vivo drug metabolism in man and its change by drugs. Maximal glucuronide formation was obtained by 1.0 g of salicylamide administered to NV; thus, this dosage was used in the present study. SAMG as percent of total salicylamide, the percent of SAMG, from 0-6 hours-urine specimens was high and constant in NV (71.3 +/- 8.3 (Mean +/- S.D.)). 0-0.08% of the total salicylamide was confirmed as free salicylamide in 0-12 hours-urine specimens of NV. The percent of SAMG of 0-6 hours-urine specimens was 57.2 +/- 8.6 in acute hepatitis, 66.6 +/- 10.9 in chronic hepatitis, and 48.6 +/- 10.7 in liver cirrhosis (mean +/- S.D.). Free salicylamide increased slightly in liver diseases. Serum bilirubin levels tended to be inversely correlated with the percent of SAMG. In most cases of Gilbert's syndrome, the percent of SAMG remained at a normal level. The percent of SAMG in cases with unconjugated hyperbilirubinemias of other geneses were almost within normal limits. Bucolome and phenobarbital increased the percent of SAMG in patients with various liver diseases. After rifampicin or phenytoin administration, the percent of SAMG of the patients with lung tuberculosis or epilepsy did not surpass that of NV.
 ...
PMID:Salycylamide glucuronide formation in liver disease and its change by drugs. 1 Feb 19

The effect of moderate cirrhosis on the bioavailability and systemic clearance of three model analgesic compounds (pethidine, pentazocine, and salicylamide) with substantial first-pass metabolism was examined in 8 cirrhotic subjects and 4 agematched healthy controls. There was a 46% decrease in the clearance of pentazocine and a 278% increase in bioavailability. The corresponding figures for pethidine were 36% and 81%. The area under the plasma curve after oral salicylamide was increased by 551% in cirrhotic subjects compared with controls. This study demonstrated that drugs with the highest hepatic clearance will have the largest relative increases in bioavailability in cirrhotic patients due to portosystemic shunting. The decrease in clearance and increase in bioavailability will have multiplicative, rather than simply additive, effects on total area under the curve and, if related, pharmacologic response.
 ...
PMID:Enhanced bioavailability and decreased clearance of analgesics in patients with cirrhosis. 44 33

The pharmacokinetic parameters of lidocaine, antipyrine and salicylamide were studied in dogs before and after construction of a portacaval shunt. The systemic availability of antipyrine was not altered significantly by the surgical procedure whereas the availability of lidocaine and salicylamide, drugs with a marked first-pass effect, was increased from 14.8 +/- 2.8 to 81.3 +/- 5.2% and from 21.8 +/- 7.8 to 57.5 +/- 2.5%, respectively. Of the 78% first-pass extraction of salicylamide, 36% is due to hepatic extraction whereas the remaining 42% is accounted for by intestinal wall extraction. The presence of a portacaval shunt also reduced the plasma clearance of lidocaine and antipyrine, but not salicylamide. The apparent volume of distribution was decreased only with salicylamide. Surgical construction of a portacaval shunt in dogs in a good model to evaluate first-pass effect. Physicians should adjust downward the dose of drugs with a first-pass effect. Physicians should adjust downward the dose of drugs with a first-pass effect in patients with a surgical portacaval shunt or endogenous portal systemic shunts such as seen in cirrhosis of the liver.
 ...
PMID:Effect of portacaval shunt on the disposition of drugs with and without first-pass effect. 119 28

Splanchnic arteriovenous differences for several intermediary metabolites of carbohydrate and lipid metabolism were determined simultaneously with hepatic blood flow in seven normal subjects, eight patients with cirrhosis, and six patients with cirrhosis after surgical portosystemic shunt ( SPSS ) after an overnight fast. Arteriovenous differences in the legs were also determined together with flux measurement. The individual turnover rates of acetoacetate (AcAc) and 3 hydroxybutyrate (beta OHB) were also determined by means of isotopic techniques. Splanchnic gluconeogenic precursors and FFA uptakes were lower in cirrhotic patients with SPSS than in normal subjects (P less than 0.05 and P less than 0.01, respectively). Splanchnic triglyceride output was also lower in cirrhotic patients with SPSS than in normal subjects (P less than 0.01), whereas no significant differences were found for AcAc, beta OHB, and glucose release. In the group of cirrhotic patients without SPSS , those patients with negligible signs of portal systemic shunt and normal splanchnic blood flow had uptake of gluconeogenic precursors and of FFA normal or higher than that of normal subjects, whereas those patients with signs of spontaneous portal systemic shunt behaved like cirrhotic patients with SPSS . Alanine release from the leg was lower in both cirrhotic patient groups. Tracer determined hepatic output of AcAc and beta OHB was higher in cirrhotic patients with SPSS (P less than 0.05). Plasma clearance rates of AcAc and beta OHB were significantly elevated in both cirrhotic patient groups. Close agreement was found between tracer and catheterization techniques in the evaluation of ketone body production in cirrhotic patients with SPSS , whereas in cirrhotic patients without SPSS tracer determined hepatic output was slightly lower, possibly because of extrahepatic splanchnic tissue ketone body uptake. In conclusion, our data in patients with cirrhosis indicate that: 1) splanchnic uptake of gluconeogenic precursors and of FFA was related to the degree of portal systemic shunt, e.g. to the degree of effective hepatic blood flow; 2) liver triglyceride but not ketone body output was decreased by the impaired FFA (and glycerol) liver uptake; 3) the higher circulating levels of gluconeogenic precursors (except alanine) and of FFA appeared at least partially due to lower hepatic removal of these metabolites; and 4) peripheral use of ketone bodies was increased and alanine release from the leg reduced in patients with cirrhosis.
 ...
PMID:Carbohydrate and lipid metabolism in cirrhosis. Evidence that hepatic uptake of gluconeogenic precursors and of free fatty acids depends on effective hepatic flow. 637 11

Nitazoxanide (NTZ) is a highly hydrophobic nitrothiazolyl-salicylamide that displays antimicrobial activity against a variety of parasites, anaerobic bacteria and viruses. More recently, its effectiveness in the pharmacotherapy of chronic hepatitis, the leading cause of liver cirrhosis and hepatocellular carcinoma (HCC), has been reported. On the other hand, the extremely low aqueous solubility of the drug challenges its administration by different routes. The present work explored for the first time the encapsulation of NTZ within pristine, lactosylated and mixed poly(ethylene oxide)-poly(propylene oxide) (PEO-PPO) polymeric micelles (PMs) of different architectures, molecular weights and hydrophilic-lipophilic balance (HLB) as a strategy to improve its aqueous solubility and to potentially target it to the liver parenchyma. The solubility was increased up to 609 times. The drug encapsulation modified the self-aggregation pattern of the different amphiphiles, resulting in a sharp growth of the micellar size. The encapsulation capacity of the lactosylated derivatives was smaller than that of the pristine counterparts, though the development of mixed PMs that combine a highly hydrophilic lactosylated amphiphile (e.g., poloxamer F127 or poloxamine T1107) that forms the micellar template and a more hydrophobic unmodified poloxamine (T904) that increases the hydrophobicity of the core resulted in the synergistic encapsulation of the drug and a substantial increase of the physical stability over time. Overall findings confirmed the extremely great versatility of the poloxamer/poloxamine mixed self-assembly systems as Trojan nanocarriers for the encapsulation of NTZ towards its targeting to the liver.
 ...
PMID:Encapsulation of the antimicrobial and immunomodulator agent nitazoxanide within polymeric micelles. 2473 46