Factors Contributing to Variability in Drug Pharmacokinetics. I. Absorption

Welling, Peter G.; Tse, Francis L. S.

doi:10.1111/j.1365-2710.1984.tb01075.x

Cited by 6 publications

(4 citation statements)

References 62 publications

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“…[89] Drug-Food Interactions Drug-food interactions are complex and dependent on the properties of the specific meal and drug, and the timing of drug ingestion in relation to the consumption of food. [90][91][92][93] Characteristics of the drug that are important include its physicochemical properties and formulation. Changing the physicochemical properties of a drug, such as the methylation of a gyrase inhibitor, may alter the effect of food on the rate of absorption.…”

Section: Fastingmentioning

confidence: 99%

Pharmacokinetic Considerations in Gastrointestinal Motor Disorders

Hebbard

Sun

Bochner

et al. 1995

Clinical Pharmacokinetics

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Although it has been recognised that alterations in gastrointestinal motility, whether induced by physiological or pathological processes, have significant effects on the pharmacokinetics of orally administered drugs, this subject has received inappropriately little attention. Studies relating to this topic have focused on healthy volunteers and animals and have largely been confined to the effects of single drug doses. There is limited information about the effects of disease on pharmacokinetics under steady-state conditions. Changes in gastrointestinal motility may affect the pharmacokinetics of orally administered drugs by altering the rate of delivery, bioavailability or mucosal absorption of the drug. In general the rate of absorption and time taken to achieve maximal plasma concentrations for well absorbed drugs may be modified by changes in gastrointestinal motility, but overall bioavailability is not usually affected. In these cases the therapeutic and clinical effects of the alteration in pharmacokinetics will, therefore, depend on which parameters are important for the action of the drug. For poorly absorbed drugs both the rate of absorption and bioavailability are likely to be altered by changes in gastrointestinal motility. However, the complex effects of food and disease, as well as the properties and formulation of any drug (solubility, ease of dispersion, delayed release formulation) often make the prediction of the magnitude, or even the direction, of any effect difficult to predict. Drugs with direct effects on gastrointestinal motility may influence their own patterns of absorption. In patients with gastrointestinal motility disorders, drugs administered in a controlled release formulation, or those with poor bioavailability, are most likely to have a poorly predictable therapeutic effect. Care should be taken to ensure that the formulation of the drug, its timing of administration in relation to meals and the use of coadministered drugs optimise, or at least ensure consistent absorption.

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Section: Fastingmentioning

confidence: 99%

Pharmacokinetic Considerations in Gastrointestinal Motor Disorders

Hebbard

Sun

Bochner

et al. 1995

Clinical Pharmacokinetics

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“…The wide spectrum of effects of different drugs precludes the application of universal rules and guidelines in drug therapy in most cases of malabsorption. Drugs, dosage forms, and various interactions should be considered individually [34], and if malabsorption exists, monitoring of therapy should be considered with venous blood assays if changes in absorption are based on bioavailability [35]. To date, this is the first assay of pregabalin in celiac disease.…”

Section: Discussionmentioning

confidence: 99%

Pregabalin Assay in a Patient with Widespread Neuropathic Pain and Late Onset Gluten Intolerance: Table 1

2011

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“…1986;Kaniwa et a1. 1988a) because the stomach becomes more distended as the volume of solution increases and this mechanical distension stimulates vagal reflexes to increase the gastric emptying rate (Nimmo 1976;Welling & Tse 1984). Solutions are emptied from the stomach more quickly than solids (Kaniwa et a1.…”

Section: Physiological Factors Affecting Drug Absorptionmentioning

confidence: 99%

Drug Absorption in Gastrointestinal Disease and Surgery

Gubbins

Bertch

1991

Clinical Pharmacokinetics

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Drug absorption from the gastrointestinal (GI) tract and the impact of GI surgery and disease on drug absorption are discussed. Recommendations are made to manage problems of drug malabsorption. Absorption from the GI tract is a first-order process described by its rate and extent. GI surgery changes the anatomy of the GI tract and alters important variables in the absorption process. In the wake of procedures which diminish small bowel surface area, the extent of absorption of phenytoin, digoxin, cyclosporin, aciclovir, hydrochlorothiazide and certain oral contraceptives is reported to be reduced. The underlying cause of the reduction is unknown. When gastric emptying time or pH are altered by surgery, the rate of drug absorption appears to be reduced. However, it is not clear which variable is more important in determining therapeutic effects. The effects of coeliac and inflammatory bowel diseases on the distribution and clearance of drugs must be considered before attributing abnormal serum concentrations of drugs to malabsorption. GI disease may slow gastric emptying and delay the complete absorption of drugs when their rate of absorption depends on gastric emptying time. Other inflammatory GI diseases such as graft-versus-host disease (GVHD) of the gut, Behçet's syndrome and scleroderma involving the GI tract may directly reduce absorption of drugs such as cyclosporin, amitriptyline, benzodiazepines, anticonvulsants, paracetamol (acetaminophen) and penicillamine. GI diseases which alter gut pH affect the absorption only of drugs with limited water solubility and pH-dependent dissolution such as ketoconazole. Clinicians should be aware of the variable absorption seen after GI disease and surgery and monitor their patients accordingly.

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Factors Contributing to Variability in Drug Pharmacokinetics. I. Absorption

Cited by 6 publications

References 62 publications

Pharmacokinetic Considerations in Gastrointestinal Motor Disorders

Pharmacokinetic Considerations in Gastrointestinal Motor Disorders

Pregabalin Assay in a Patient with Widespread Neuropathic Pain and Late Onset Gluten Intolerance: Table 1

Drug Absorption in Gastrointestinal Disease and Surgery

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