Similar pharmacokinetics of tegaserod (HTF 919) in patients with constipation- and diarrhea-predominant irritable bowel syndrome

Appel‐Dingemanse, Silke; Rawls, James; Heggland, Joan; Campestrini, Joelle; Séchaud, Romain

doi:10.1016/s0016-5085(00)80460-6

Cited by 3 publications

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“…In healthy volunteers and in patients with IBS-C and IBS with diarrhea (IBS-D), similar multiple-dose PK of tegaserod was observed, when the food effect was considered [ 117 , 119 , 122 ]. For the 6 mg BID dose in patients with IBS-C and IBS-D, AUC τ and C max,ss were 30 to 50%, lower than those in healthy individuals following administration in fasting conditions [ 121 ].…”

Section: Tegaserod and Ibs-cmentioning

confidence: 79%

“…For the 6 mg BID dose in patients with IBS-C and IBS-D, AUC τ and C max,ss were 30 to 50%, lower than those in healthy individuals following administration in fasting conditions [ 121 ]. For patients with IBS-C and IBS-D the type of bowel function abnormality has no impact on the PK of tegaserod (Table 4 ) [ 117 , 119 , 122 - 124 ].…”

Section: Tegaserod and Ibs-cmentioning

confidence: 99%

“… *Data are referred to a study involving 54 patients for C-IBS or 32 patients for D-IBS [ 122 ]; § Data are referred to a study involving 18 subjects (11 male and 7 female) [ 121 ]. …”

Section: Fig (1)mentioning

confidence: 99%

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Tegaserod for the Treatment of Irritable Bowel Syndrome

Madia

Messore

Saccoliti

et al. 2020

AIAAMC

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Background: Tegaserod (Zelnorm®) is a 5-hydroxytryptamine (serotonin) type 4 receptor agonist for the treatment of hypomotility disorders of the lower gastrointestinal tract associated with the irritable bowel syndrome with constipation (IBS-C). Objective: The authors provide the reader with a better understanding on tegaserod mechanism of action, on its pharmacodynamics and pharmacokinetic properties, on safety and tolerability, with a summary of the key published clinical trials conducted in patients with IBS. Its effects on colon inflammation have also been described. Results: Tegaserod was withdrawn in 2007 due to increased risks of cardiovascular adverse effects. The manufacturer denied this, because pre-existing cardiovascular disease or risk factors were attributed to all affected patients. Thus, no causal relationship between tegaserod use and cardiovascular events was clearly shown. A matched case-control study of tegaserod-treated with untreated patients found no association between tegaserod and adverse cardiovascular outcomes. Despite its adverse effects, tegaserod resulted to be effective in treating chronic constipation in adult women aged < 65 years with IBS-C, while the safety and effectiveness of tegaserod in men with IBS-C have not been established. Tegaserod was resubmitted to the Food and Drug Administration in 2018 for use in a low-risk population. Moreover, tegaserod has also been shown to improve symptoms, enhance gastric accommodation and significantly attenuate visceral pain arising from the colon in functional dyspepsia patients. Treatment with tegaserod seems also to exert a protective effect in inflamed colons, reducing the severity of colitis in animal models.

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Section: Tegaserod and Ibs-cmentioning

confidence: 79%

Section: Tegaserod and Ibs-cmentioning

confidence: 99%

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Tegaserod for the Treatment of Irritable Bowel Syndrome

Madia

Messore

Saccoliti

et al. 2020

AIAAMC

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Tegaserod

Lacy

2002

Journal of Clinical Gastroenterology

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Tegaserod is a medication that has been shown to be of benefit in women with irritable bowel syndrome (IBS) associated with abdominal pain, bloating, and constipation. Tegaserod is a selective serotonin receptor subtype 4 partial agonist designed to interact with the network of cells and nerves throughout the gastrointestinal tract that use serotonin. Tegaserod has been shown to modulate both gastrointestinal motility and visceral sensitivity. Specifically, it increases the peristaltic reflex and decreases visceral sensitivity. Clinical studies have shown that tegaserod improves symptoms of abdominal pain, bloating, and constipation in women with IBS. This article discusses the role of serotonin in gastrointestinal tract physiology, the structure and pharmacokinetic profile of tegaserod, and clinical applications of this new drug.

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Clinical Pharmacokinetics of Tegaserod, a Serotonin 5-HT4 Receptor Partial Agonist with Promotile Activity

Appel‐Dingemanse

2002

Clinical Pharmacokinetics

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Tegaserod, a selective serotonin (5-hydroxytryptamine; 5-HT) 5-HT(4) receptor partial agonist, is indicated in patients with irritable bowel syndrome (IBS) who identify abdominal pain or discomfort and constipation as their predominant symptoms. Tegaserod at dosages of 1 to 12 mg/day exerts pharmacodynamic actions in the upper and the lower gastrointestinal tract, accelerating small bowel and colonic transit in patients with IBS. Tegaserod is rapidly absorbed following oral administration; peak plasma concentrations (C(max)) are reached after approximately 1 hour. Absolute bioavailability is about 10% under fasted conditions. Food reduces the bioavailability of tegaserod by 40 to 65% and the C(max) by 20 to 40%. Systemic exposure to tegaserod is not significantly altered at neutral gastric pH compared with the fasted state (pH 2). Tegaserod is approximately 98% bound to plasma proteins, primarily to alpha(1)-acid glycoprotein, and has a volume of distribution at steady-state of 368 +/- 223L. Tegaserod is metabolised mainly via two pathways. The first is a presystemic acid-catalysed hydrolysis in the stomach followed by oxidation and conjugation which produces the main metabolite of tegaserod, 5-methoxyindole-3-carboxylic acid glucuronide (M 29.0). This metabolite has negligible affinity for 5-HT(4) receptors and is devoid of promotile activity. The second is direct glucuronidation which leads to generation of three isomeric N-glucuronides. The plasma clearance of tegaserod is 77 +/- 15 L/h, with an estimated terminal half-life of 11 +/- 5 hours following intravenous administration. Approximately two-thirds of the orally administered dose of tegaserod is excreted unchanged in faeces, with the remainder excreted in urine, primarily as M 29.0. The pharmacokinetics of tegaserod are dose-proportional over the range 2 to 12mg given twice daily for 5 days, with no relevant accumulation. The pharmacokinetics of tegaserod in patients with IBS are comparable to those in healthy individuals, and similar between men and women. No dosage adjustment is required in elderly patients or those with mild to moderate hepatic or renal impairment. Tegaserod should not be used in patients with severe hepatic or renal impairment. No clinically relevant drug-drug interactions with tegaserod have been identified. In vivo drug-drug interaction studies with theophylline [a cytochrome P450 (CYP) 1A2 prototype substrate], dextromethorphan (a CYP2D6 prototype substrate), digoxin, warfarin and oral contraceptives have indicated no clinically relevant interactions and no requirement for dosage adjustment.

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Similar pharmacokinetics of tegaserod (HTF 919) in patients with constipation- and diarrhea-predominant irritable bowel syndrome

Cited by 3 publications

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Tegaserod for the Treatment of Irritable Bowel Syndrome

Tegaserod for the Treatment of Irritable Bowel Syndrome

Tegaserod

Clinical Pharmacokinetics of Tegaserod, a Serotonin 5-HT4 Receptor Partial Agonist with Promotile Activity

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