Biliary Excretion of Diazepam in Man

Eustace, Patricia; Hailey, D.M.; Cox, AlanG.; Baird, E.S.

doi:10.1093/bja/47.9.983

Cited by 7 publications

(4 citation statements)

References 5 publications

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“…The mechanism responsible for the fluctuations in plasma diazepam and N-desmethyldiazepam is not known. Enterohepatic circulation of diazepam and its metabolites is unlikely to be the cause of fluctuations because a significant and clinically relevant enterohepatic circulation does not occur (Eustace, Hailey & Baird, 1975;Klotz, Antonin & Bieck, 1976b;Mahon, Inaba, Umeda, Tsutsumi & Stone, 1976;Sellman, Hurme & Kanto, 1977). Changes in total body clearance could not be responsible for coincident increases in diazepam and N-desmethyldiazepam total concentrations.…”

Section: Discussionmentioning

confidence: 96%

Diurnal variations in plasma diazepam concentrations associated with reciprocal changes in free fraction.

Naranjo¹,

Sellers²,

Hg³

et al. 1980

Brit J Clinical Pharma

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The characteristics and mechanism of fluctuations in diazepam and N-desmethyldiazepam concentrations and diazepam free fraction were studied in six volunteers, who received diazepam (10 mg, i.v. over 20 min) and in five chronic diazepam users. 2 Within a day total diazepam and N-desmethyldiazepam concentrations varied significantly (P<0.001) and were lower than predicted between 23.00 and 08.00 h and higher by 09.00 h. In contrast, diazepam free fraction also varied significantly (P<0.001) and was highest between 23.00 and 08.00 h and lower by 09.00 h. Coincident increases in total diazepam concentrations (P < 0.005) and decreases in diazepam free fraction were associated with food intake (P<0.05). 3 The coincident diurnal variations in diazepam and N-desmethyldiazepam concentrations and the negative correlation between total diazepam concentration and diazepam free fraction (r= -0.73, P<0.001) suggest that the mechanism of the fluctuations is intravascular and tissue redistribution rather than effect on drug biotransformation. 4 These variations may introduce large between and within investigator experimental differences in the determination of kinetic parameters. Free drug concentration varies over the day, and within day variations in clinical effect may be observed.

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Section: Discussionmentioning

confidence: 96%

Diurnal variations in plasma diazepam concentrations associated with reciprocal changes in free fraction.

Naranjo¹,

Sellers²,

Hg³

et al. 1980

Brit J Clinical Pharma

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“…These diseases increase the risk of surgery and affect patients' prognosis, and even lead to perioperative death 9 . Surgical treatment strategies for elderly patients diagnosed with choledocholithiasis combined with cholecystolithiasis include laparoscopic choledocholithotomy, cholecystectomy and T-tube drainage 10 . Although laparoscopic surgery is less invasive, T-tube drainage in the biliary tract can still cause pain and other complications 11 .…”

Section: Introductionmentioning

confidence: 99%

The effect of the laparoscopic primary suture of the common bile duct in elderly patients: a retrospective study

Liu

Wang

Liu

et al. 2019

Preprint

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Background Traditionally, Surgical treatment strategies for elderly patients diagnosed with choledocholithiasis combined with cholecystolithiasis include laparoscopic choledocholithotomy, cholecystectomy, and T-tube drainage. However, T-tube drainage in the biliary tract can still cause pain and other complications. This study was designed to compare the primary closure of choledochotomy and the use of T-tube after laparoscopic choledochotomy to determine whether primary suture can be as feasible and safe as suture with T-tube drainage in elderly patients. Methods From January 2017 to January 2018, 85 patients were selected to undergo laparoscopic surgery. They were divided into two groups: primary suture group (n=56) and T tube group (n=29). Preoperative data, intraoperative index, postoperative complications were recorded. Results There were no differences in preoperative data in both groups. Compared with the T-tube group, the postoperative total drainage volume on the first day and patients of residual stones were fewer, and all drainage tube extubation time was shorter in the primary suture group. And there were statistically significant differences in postoperative TBIL between the two groups. There were no pressure sores, hypostatic pneumonia, deep vein thrombosis, serious complications of heart, lung and brain and even death in both groups. Conclusion Only if accurate preoperative risk assessment and strict treatment of basic diseases in elderly patients, intraoperative fine suture of the common bile duct, primary suture in elderly patients are feasible, safe, and valid after laparoscopic choledochotomy for verification of ductal clearance.

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“…Studies demonstrating a rebound in plasma diazepam levels have all involved total (protein-bound and free together) diazepam levels ( BAIRD & HAILEY 1972;KORTTILA & LINNOILA 1974;LINNOILA et al 1975;EUSTACE et al 1975;KORTTILA et al 1976), but no one has reported on the fluctuations in free diazepam levels, which according to current concept are responsible for drug actions (CROSSLAND 1970). TSUTSUMI et al (1975) showed in vitro that sodium laurate displaced as much as 13 to 14% of therapeutic concentrations of diazepam from the binding site in albumin.…”

mentioning

confidence: 99%

“…In the case of intravenous diazepam the recurrence of clinical sedation and the subsequent impairment of psychomotor skills after food intake is due rather to a re-mobilization of diazepam from its storage site than to its enterohepatic circulation (EUSTACE et al 1975;KORTTILA et al 1976) or changes in its binding to serum proteins.…”

mentioning

confidence: 99%

Unchanged Protein Binding and the Increase of Serum Diazepam Levels after Food Intake

Korttila

Kangas

1977

Acta Pharmacologica et Toxicologica

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Seven subjects received diazepam 0.3 mg/kg intravenously twice with a 2‐week interval between the doses. The subjects ingested a fatty or carbohydrate meal in a cross‐over fashion 4 hours after the injection on both experimental days. Venous blood samples were drawn 2, 3, 4, 5 and 6 hours after the injection of diazepam for measurement of the serum levels of total and free (unbound) diazepam, N‐desmethyldiazepam, and free fatty acids. Serum levels of diazepam decreased progressively with time until the food intake, after which a significant (P < 0.01) postprandial increase (average 23 %) occurred with both diets as compared to the preprandial levels at 4 hours (average 240 ng/ml). Serum levels of free fatty acids decreased significantly both after a fatty (P < 0.01) and a carbohydrate (P < 0.05) meal. Diazepam was extensively (96 to 98 %) bound to proteins and no changes in its protein binding was found. It is concluded that the late impairment of psychomotor skills that occurs with an increase in the diazepam serum level after its intravenous administration is due rather to its re‐mobilization from a storage site than to variations in its protein binding.

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Biliary Excretion of Diazepam in Man

Cited by 7 publications

References 5 publications

Diurnal variations in plasma diazepam concentrations associated with reciprocal changes in free fraction.

Diurnal variations in plasma diazepam concentrations associated with reciprocal changes in free fraction.

The effect of the laparoscopic primary suture of the common bile duct in elderly patients: a retrospective study

Unchanged Protein Binding and the Increase of Serum Diazepam Levels after Food Intake

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