Reduction in serum bilirubin by phenobarbital in adult unconjugated hyperbilirubinaemia

Whelton, M. J.; Krustev, L; Billing, Barbara H.

doi:10.1016/0002-9343(68)90017-x

Cited by 39 publications

(9 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Effect of phenobarbitone administration Phenobarbitone administration to patients with Gilbert's syndrome resulted in lowering of the plasma bilirubin levels, as reported elsewhere (Black & Sherlock, 1970). In agreement with other studies of congenital non-haemolytic jaundice (Whelton, Krustev & Billing, 1968 ;Crigler & Gold, 1969;Arias et al, 1969), phenobarbitone therapy was strikingly successful in lowering the plasma bilirubin; it was noted that 4 weeks:therapy to patients 15 and 16 failed to lower plasma levels entirely to normal, and indeed 9 months therapy with this medication at the same dose level had no further effect. The plasma bilirubin level of the patient with haemolytic jaundice was slightly lower at the end of the 2 weeks therapy with phenobarbitone than at the outset, but had not fallen outside the range observed in this patient over a prolonged period of observation, during which he received no medication.…”

Section: Plasma ['4c]bilirubin Clearance Curves Before Phenobarbitonesupporting

confidence: 90%

“…A similar effect with glutethimide has been shown in experimental animals by . While Yaffe, Levy, Matsuzawa & Baliah (1966), Whelton et al (1968) andCrigler &Gold (1969) have suggested that the administration of phenobarbitone to patients, whose unconjugated hyperbilirubinaemia resulted from decreased hepatic bilirubin glucuronyl transferase activity, might lower plasma bilirubin, by increasing the amount of enzyme, no previous data on enzyme levels in this situation have been presented. Only Crigler & Gold (1969) have previously reported on the effects of phenobarbitone on bilirubin clearance (in a child with congenital non-haemolytic jaundice).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Effect of Phenobarbitone on Plasma [14C]Bilirubin Clearance in Patients with Unconjugated Hyperbilirubinaemia

et al. 1974

Self Cite

View full text Add to dashboard Cite

1. The clearance of a tracer dose of [14C]bilirubin from the plasma was studied in patients with Gilbert's syndrome, congenital non-haemolytic jaundice, haemolytic jaundice and in normal subjects. Clearance was significantly impaired in the patients with Gilbert's syndrome and in those with congenital non-haemolytic jaundice when compared with the normal subjects, and was normal in the patient with haemolytic jaundice. 2. Treatment for 2 weeks with phenobarbitone (180 mg/day) lowered the plasma bilirubin concentration and improved all indices of plasma clearance of the isotope in patients with Gilbert's syndrome, so that they became indistinguishable from those of normal subjects. The improvement in plasma [14C]bilirubin clearance in these patients was associated with modest increases in hepatic bilirubin glucuronyl transferase in some subjects. 3. Phenobarbitone treatment improved plasma bilirubin concentrations and plasma [14C]bilirubin clearance in patients with congenital non-haemolytic jaundice, so that they resembled those seen in patients with untreated Gilbert's syndrome. Despite this improvement hepatic bilirubin glucuronyl transferase activity remained undetectable. 4. These results are compatible with the hypothesis that Gilbert's syndrome is a manifestation of a relative deficiency of hepatic bilirubin glucuronyl transferase, and differs from congenital non-haemolytic jaundice only in severity.

show abstract

Section: Plasma ['4c]bilirubin Clearance Curves Before Phenobarbitonesupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Effect of Phenobarbitone on Plasma [14C]Bilirubin Clearance in Patients with Unconjugated Hyperbilirubinaemia

et al. 1974

Self Cite

View full text Add to dashboard Cite

show abstract

“…The absence of changes in human hepatocytes after short-term administration of phenobarbital in patients with normal liver resulted from previous observations made on a non-quantitative basis (Jezequel and Orlandi, 1972;Jezequel, 1974) and also from morphometric studies in an infant with the Crigler-Najjar syndrome (Gotze, Sidiropoulos, Hess, and Berthelot, 1972). This appears in contradiction to other reports (Whelton, Krustev, and Billing, 1968;Crigler and Gold, 1969). The fact that the normal amount and distribution of the SER before treatment have not always been taken into consideration may explain apparent discrepancies.…”

Section: Discussioncontrasting

confidence: 99%

A morphometric study of the endoplasmic reticulum in human hepatocytes : Correlation between morphological and biochemical data in subjects under treatment with certain drugs

Jézéquel¹,

Koch²,

Orlandi³

1974

Gut

View full text Add to dashboard Cite

SUMMARYThe distribution of the endoplasmic reticulum in human hepatocytes is defined in quantitative terms using the techniques of morphometry. The subjects of the study are liver biopsies from normal, untreated subjects and patients being treated with various drugs. In contrast to rat hepatocytes, the amount of smooth endoplasmic reticulum (SER) in man exceeds that of the rough endoplasmic reticulum (RER) and accounts for 76.3 % of the total endoplasmic reticulum. This is to be taken into consideration in pharmacological or toxicological studies. In addition, two components of the SER have been identified: more prominent is the type 1 or vesicular which has a regular honeycomb pattern, made up ofcisternae with patent lumina and a mean width of 1500 A; the type 2, or non-vesicular, occurs in discrete foci of densely packed smooth membranes with a spacing of about 140 A. In subjects under short-term treatment with Benzodiazepin (diazepam) the RER remained unchanged but the SER membranes were significantly increased with a remarkable, twoto threefold increase of the SER type 2 in three out of four patients. A rise in incorporation of 14C-acetate into digitonin-precipitable sterols as measured in liver biopsy material was also noted in these three patients. The suggestion is made that the SER 2 represents the newly formed membranes whereas the SER 1 would represent 'adult' membranes. No changes were observed in two patients under short-term treatment with phenobarbital or Dilantin.A few morphometric studies have already been conducted on animal liver in normal (Loud, 1968;

show abstract

“…In human liver, the evidence for such a link between the biochemical and morphological expression of induction is still scanty. An increase in the amount of smooth endoplasmic reticulum has been said to occur after phenobarbital (Whelton, Krustev, and Billing, 1968;Crigler and Gold, 1969) or alcohol administration (Rubin, Hutterer, and Lieber, 1968;) but it does not seem that morphological changes are qualitatively or quantitatively similar to those observed in animals.…”

Section: Discussionmentioning

confidence: 99%

Changes of the smooth endoplasmic reticulum induced by rifampicin in human and guinea-pig hepatocytes

Jézéquel¹,

Orlandi²,

Tenconi³

1971

Gut

View full text Add to dashboard Cite

SUMMARY Rifampicin induces a proliferation of the smooth endoplasmic reticulum in guinea-pig and human hepatocytes. This may support the hypothesis of enhancement of drug-metabolizing enzymes induced by the drug. However, the pattern of proliferation is not similar in man and in guinea-pig hepatocytes. Some caution is needed in the study of enzyme induction in man and in extrapolations fromn animal to human data. Meyer-Brunot, 1968;Curci, Ninni, and Iodice, 1969). On the other hand, repeated administration of rifampicin causes a decrease in the half-life and a fall in blood levels of the drug (Curci, Ninni, and Iodice, 1969;Furesz, 1970) together with an increase in biliary excretion of the antibiotic (Furesz, 1970 suspended in 1 % Methocel at a concentration of 16 mg/ml through a gastric tube. After two days of treatment three animals, after five days five, and after 10 days three animals were killed. Four animals received only 1 % Methocel at a dose of 0.5 ml/100 g body weight: at two days one was killed, at five days two,and at 10days one animal.Two animals did not receive any treatment. These animals were killed by section of the carotid; the abdomen was opened immediately and fragments of liver were processed for light and electron microscopy. PATIENTSTwo patients received 20 mg/kg/day rifampicin (Rifadin, Lepetit-Milan) and four 10 mg/kg/day. A liver biopsy was taken after two days of treatment. A control biopsy before treatment was obtained in three of these patients.One patient received 10 mg/kg/day for five days followed by 16 mg/kg/day for two days. A liver biopsy was taken at the end of the seven days. PROCESSING THE MATERIALFor light microscopy fragments of liver were fixed in 4% formalin, embedded in paraffin, and stained with haematoxylin-eosin. For electron microscopy, 1 mm3 fragments were fixed for one and a half hours in 1 % osmic acid in phosphate buffer pH 7.4. After dehydration with alcohol the fragments were embedded in an Epon/Araldite mixture.The blocks were cut with an LKB Ultrotome III 984

show abstract

Reduction in serum bilirubin by phenobarbital in adult unconjugated hyperbilirubinaemia

Cited by 39 publications

References 14 publications

Effect of Phenobarbitone on Plasma [14C]Bilirubin Clearance in Patients with Unconjugated Hyperbilirubinaemia

Effect of Phenobarbitone on Plasma [14C]Bilirubin Clearance in Patients with Unconjugated Hyperbilirubinaemia

A morphometric study of the endoplasmic reticulum in human hepatocytes : Correlation between morphological and biochemical data in subjects under treatment with certain drugs

Changes of the smooth endoplasmic reticulum induced by rifampicin in human and guinea-pig hepatocytes

Contact Info

Product

Resources

About