The effect of jejunoileal bypass on the pharmacokinetics of digoxin in man.

Marcus, F I; Quinn, Elizabeth; Horton, Herschella; Jacobs, Shannon; Pippin, Susan; Stafford, Marvin; Zukoski, Charles F.

doi:10.1161/01.cir.55.3.537

Cited by 31 publications

(12 citation statements)

References 14 publications

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“…However, a strong correlation was found between AUe or peak serum digoxin concentrations and the length of the remaining jenunum. These results were not sustained by Marcus et al (1977) or Krausz et al (1979), who did not find any significant differences in digoxin absorption before and after small bowel resections. Heizer et al (1971) found a slightly reduced digoxin absorption in a patient with jejunocolostomy and in patients with idiopathic malabsorption, while the absorption was normal in patients with gastrectomy even when the duodenal mucosa was bypassed as in the Billroth II operation (Beermann et aI., 1973).…”

Section: Discussionmentioning

confidence: 73%

“…Drug kinetics might thus be affected by the shunt operation in several ways: exclusion ofa section of varying length of the small intestine might affect drug absorption; the weight loss will change drug distribution; and metabolism could be decreased by postoperatively induced hepatic disease. However, pharmacokinetic studies in intestinal bypass patients dealing with antiepileptic drugs (Kennedy and Wade, 1979;Peterson and Zweig, 1974), anti- pyrine (Andreasen et a!., 1977), digoxin (Gerson et a!., 1980;Marcus et a!., 1977) and antituberculous drugs (Bruce and Wise, 1977;Polk et aL, 1978;Wasson and Harris, 1976) have produced conflicting results, which might be partly explained by differences in the experimental design. The most frequently used procedure -comparison of an operated and a normal control group -introduces a great interindividual error, and drug administration by the oral-route only makes it impossible to estimate the absolute bioavailability of the agents involved.…”

mentioning

confidence: 99%

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Ampicillin and Propylthiouracil Pharmacokinetics in Intestinal Bypass Patients Followed Up to a Year after Operation

Kampmann

Klein

Lumholtz

et al. 1984

Clinical Pharmacokinetics

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The pharmacokinetics of ampicillin and prophylthiouracil were studied in 6 and 9 patients, respectively, before and several times up to a year after a shunt operation for extreme obesity. The drugs were given intravenously and orally making it possible to estimate the absolute bioavailability. The bioavailability of propylthiouracil (about 80%) was unchanged by the surgical procedure but the fraction of ampicillin (given as pivampicillin) absorbed decreased from a preoperative value of 109 +/- 44% to 44 +/- 30% 12 months after the bypass operation. Volumes of distribution transiently decreased in the postoperative period for ampicillin. Clearance was initially reduced for both ampicillin and propylthiouracil after operation but returned to normal values a year later. Half-lives of both drugs were unchanged. These results are compared with previous data on pharmacokinetics in intestinal shunt patients and a tabular review is presented. Although no general rules presently emerge from the data available, it seems prudent to closely monitor intestinal shunt patients on drug therapy by both laboratory and clinical methods.

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Section: Discussionmentioning

confidence: 73%

mentioning

confidence: 99%

Ampicillin and Propylthiouracil Pharmacokinetics in Intestinal Bypass Patients Followed Up to a Year after Operation

Kampmann

Klein

Lumholtz

et al. 1984

Clinical Pharmacokinetics

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“…Krausz et al (1979) found that digoxin absorption was not impaired in a patient with complete small bowel resection except for the proximal 15cm of the jejunum. Furthermore, Marcus et al (1977) found no differences in digoxin absorption in 7 patients before and after jejunoileal bypass. Thus, these surgical interventions have little if any effect on the extent of digoxin absorption.…”

Section: Effect Of Surgically-induced Gastrointestinal Abnormalities mentioning

confidence: 77%

Disease-related Alterations in Cardiac Glycoside Disposition

Ochs¹,

Greenblatt

Bodem

et al. 1982

Clinical Pharmacokinetics

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The eJJects of diseases involving the kidney, gastrointestinal tract, thyroid, and cardiovascular system on the disposition of cardiac glycosides are reviewed.The glycosides ouabain and digoxin are cleared predominantly by renal excretion of the intact drugs. Not surprisingly, total clearance (if these two compounds is reduced in patients with reduced creatinine clearance. Similarly, steady-state serum concentrations of digoxin at any given dose become higher as renal function declines. However, individual variability is considerable, thereby limiting the utility (if dosage schemes based on nomograms or equations. A further complication is Ihal tissue distribution (if digoxin is altered in renal inSI!fficiency, so that serum concentrations take on u different meaning in patients with renal failure. In the ca.~e (if digitoxin, renal clearance accounts for only part of the total clearance. A clear relationship between creatinine clearance and total digitoxin clearance has not yet been established. However, digitoxin protein binding is reduced in renal insufficiency, requiring a change in the clinical interpretation (if total (free plus bound) digitoxin serum concentrations in such patients. Although digoxin absorption may be impaired in patients with serious malabsorption syndromes, most studies have demonstrated normal or near normal absorption despite gastrointestinal disease or extensive ablative surgery. Hepatic cirrhosis does not alter the pharmacokinetics of digoxin, but is associated with impaired demethylation of ~-methyldigoxin (medigoxin). Although hepatic biotran~formation accounts for a substantialfraction (if the total clearance of digitoxin, disappearance (if digitoxin from the plasma is, if anything, more rapid in patients with liver disease as opposed to healthy controls.Clearance (if both digitoxin and digoxin varies in direct relation to thyroid function; clearance is increased and the ha(f-l!fe shortened in thyrotoxicosis, and the reverse is truefor hypothyroidism. This may be explained by parallel changes in creatinine clearance, but further studies are needed to d~fine the mechanism (if alterations in glycoside clearance in relation to thyroid function.Continuing re.finement of analytical and pharmacokinetic techniques will lead to rapid progress in research in this area, and a need for continuing re-evaluation of the state of the art.

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“…Likewise, that of phenytoin was significantly lowered (Kennedy & Wade, 1979). This was not the case for digoxin (Marcus et al, 1977), phenazone (Andreasen et al, 1977), ampicillin and propylthiouracyl (Klein et al, 1977).…”

Section: Discussionmentioning

confidence: 99%

Study of the bioavailability of pindolol in malabsorption syndromes.

Evard¹,

Aubry²,

Quintrec³

et al. 1984

Brit J Clinical Pharma

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Pindolol kinetics and bioavailability were studied after a single dose (oral 5 mg; intravenous 3 mg) in nine patients with malabsorption (two with villous atrophies, seven with short bowel syndromes) and in six healthy volunteers. After oral administration no significant differences were observed in bioavailability (59.4 ± 6.2% in patients vs 79.5 ± 8.6% in controls) and for most plasma and urinary pharmacokinetic parameters between the experimental and control groups as a whole. However, detailed analysis revealed decreased absorption for pindolol in two out of nine patients. After i.v. administration, apparent distribution volume was smaller (V: 2.10 ± 0.25 1 kg-' vs 3.05 + 0.31 1 kg-') and global elimination constant was larger (ke: 1.43 + 0.46 h-1 vs 0.56 + 0.10 h-1), in patients with malabsorption than in controls (P < 0.05). The smaller weight of patients and pharmacokinetic modifications due to the pathology could account for this.

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The effect of jejunoileal bypass on the pharmacokinetics of digoxin in man.

Cited by 31 publications

References 14 publications

Ampicillin and Propylthiouracil Pharmacokinetics in Intestinal Bypass Patients Followed Up to a Year after Operation

Ampicillin and Propylthiouracil Pharmacokinetics in Intestinal Bypass Patients Followed Up to a Year after Operation

Disease-related Alterations in Cardiac Glycoside Disposition

Study of the bioavailability of pindolol in malabsorption syndromes.

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