Persistence of Antibiotics in Blood of Patients With Acute Renal Failure. Ii. Chloramphenicol and Its Metabolic Products in the Blood of Patients With Severe Renal Disease or Hepatic Cirrhosis*†

Kunin, Calvin M.; Glazko, Anthony J.; Finland, Maxwell

doi:10.1172/jci103928

Cited by 159 publications

(33 citation statements)

References 23 publications

(14 reference statements)

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“…There is a growing literature on the influence of liver disease on drug disposition, with prolongation in the TiA being reported for antipyrine (Branch et al, 1973), phenylbutazone (Levi, Sherlock & Walker, 1968), carbenicillin (Hoffman, Cestero & Bullock, 1970), chloramphenicol (Kunin, Glazko & Finland, 1959) and rifamycin (Acocella, Bonelloa, Garimoldi, Mainardi, Tocini & Nicolis, 1972) The high clearance of (+)-propranolol found in normal subjects, similar to those previously reported , correlated with and was numerically similar to the clearance of ICG. Although one drug is metabolized and the other actively transported to the bile, their hepatic extraction ratios must have been equally high so that the clearance values represented were a slight underestimate of liver blood flow.…”

Section: Discussionsupporting

confidence: 81%

A study of factors influencing drug disposition in chronic liver disease, using the model drug (+)‐propranolol.

Ra¹,

James²,

Read³

1976

Brit J Clinical Pharma

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The pharmacokinetics, following i.v. administration of (+)‐propranolol (40 mg) have been compared to in vitro measurement of protein binding and biochemical parameters of liver function in six normal subjects and twenty patients with stable chronic liver disease. The clearance of (+)‐ propranolol decreased with evidence of increasing severity of impairment of liver function correlating significantly with a fall in serum albumin, a rise in bilirubin and a prolongation in prothrombin index. The clearance of (+)‐propranolol correlated with and was numerically similar to the clearance of indocyanine green in normal subjects and also in patients with chronic liver disease. Protein binding was decreased in chronic liver disease, but this change was not related to changes in plasma proteins. In normal subjects and patients without ascites the volume of distribution increased with decreases in protein binding. Ascites was associated with a further increase in the volume of distribution. The considerable variation in half‐life largely depends on changes in liver blood flow, the degree of protein binding and the plasma protein pool size.

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Section: Discussionsupporting

confidence: 81%

A study of factors influencing drug disposition in chronic liver disease, using the model drug (+)‐propranolol.

Ra¹,

James²,

Read³

1976

Brit J Clinical Pharma

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“…Therefore, a decrease in renal excretion of diflunisal glucuronides with a resultant delay in the elimination rate of these metabolites from plasma is to be anticipated and has been found in the present study in patients with renal function impairment (Figure 2 (Reidenberg, 1977). The elimination half-life of three drugs that are predominantly eliminated in man by glucuronidation such as chloramphenicol (Kunin, Glazko & Finland, 1959), acetaminophen (Lowenthal, 0ie, Van Stone, Briggs & Levy, 1976) and lorazepam It is generally recognized that the extent to which decreased renal function influences drug elimination is a function of the percentage of circulating drug cleared unchanged through the kidney. This general statement, however, is not applicable in the case of diflunisal as shown by the present investigation.…”

Section: Discussionsupporting

confidence: 54%

Biotransformation of diflunisal and renal excretion of its glucuronides in renal insufficiency.

Verbeeck¹,

Tjandramaga²,

Mullie³

et al. 1979

Brit J Clinical Pharma

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A single oral dose of 500 mg diflunisal was administered to control subjects and patients with varying degrees of renal insufficiency to estimate the disposition kinetics of this drug. 2 Diflunisal and the sum of its ester and ether glucuronides conjugates were measured fluorimetrically.3 In normals terminal plasma half-lives (Tip) of diflunisal and its glucuronides were very similar:10.8 h and 11.8 h respectively. The finding that plasma half-life was shortened with declining diflunisal plasma levels suggests capacity-limited elimination. 4 In subjects with normal renal function 78.6 + 2.7% of the administered dose was recovered in 72 h urine, mainly as the glucuronide conjugates. SWith increasing degree of renal function impairment Tip of diflunisal was progressively prolonged up to ten times normal probably due to slowed biotransformation. This was associated with increasing retention of the conjugated metabolites in plasma due to marked reduction of the urinary excretion of the glucuronide conjugates. 6 The apparent volume of distribution of diflunisal was very small in normals (7.3 ± 0.4 1) and was significantly increased in patients with renal insufficiency (up to 16.2 + 2.2 1). 7 Diflunisal elimination studies performed during haemodialysis did not reveal any significant change in diflunisal plasma half-time. In vivo ultrafiltration studies during haemodialysis have shown that diflunisal is 98-99% plasma protein bound in uraemic patients. 8 The present study indicates that although diflunisal is primarily eliminated by biotransformation,

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“…The major involvement of the liver in the above metabolism of diazepam (10, U) would suggest that hepatic dysfunction might alter the drug's disposition and elimination, as' reported for other extensively metabolized drugs (12)(13)(14)(15)(16)(17)(18)(19)(20). Such a finding would be contrary to the general clinical impression that diazepam is a safe therapeutic' agent and a sedative of choice in patients with liver disease, a concept based on the observations that there' is no prolongation of the sedative effect or abnormality in the electroencephalographic pattern in such individuals after the administration of a single dose of the drug (21).…”

mentioning

confidence: 97%

The effects of age and liver disease on the disposition and elimination of diazepam in adult man.

Klotz¹,

Avant²,

Hoyumpa³

et al. 1975

J. Clin. Invest.

644

104

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Persistence of Antibiotics in Blood of Patients With Acute Renal Failure. Ii. Chloramphenicol and Its Metabolic Products in the Blood of Patients With Severe Renal Disease or Hepatic Cirrhosis*†

Cited by 159 publications

References 23 publications

A study of factors influencing drug disposition in chronic liver disease, using the model drug (+)‐propranolol.

A study of factors influencing drug disposition in chronic liver disease, using the model drug (+)‐propranolol.

Biotransformation of diflunisal and renal excretion of its glucuronides in renal insufficiency.

The effects of age and liver disease on the disposition and elimination of diazepam in adult man.

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