Physiologic considerations in drug absorption from the gastrointestinal tract

Golub, Allyn L.; Frost, R. Wayne; Betlach, Charles J.; González, Manuel A.

doi:10.1016/0091-6749(86)90047-3

Cited by 50 publications

(33 citation statements)

References 24 publications

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“…The authors concluded that posture influences the intragastric distribution of liquids due to the effect of gravity such that, for anatomical reasons, in the left lateral (= "pylorus up") and supine posture, gravity cannot accelerate gastric emptying. Normally, the liquid is emptied according to a first-order process (exponentially): the larger the volume, the faster the emptying [3].…”

Section: Effects Of Posture On the Gastric Residence Time Of Fluids Amentioning

confidence: 99%

Influence of posture on pharmacokinetics

Queckenberg

Fuhr

2008

Eur J Clin Pharmacol

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Introduction Body position may influence physiological characteristics, such as perfusion, gastrointestinal function and plasma volume. These characteristics may interact with key factors determining the pharmacokinetics of drugs (dissolution, absorption, distribution, metabolism, excretion). Objectives Based on a systematic literature search, current data on the effect of posture on physiological characteristics and/or pharmacokinetics are summarized, and the relevance of possible effects, such as those presenting in clinical practice and clinical pharmacokinetic studies, is assessed. Results Postures which favour rapid gastric emptying (sitting, standing, recumbent right) accelerate the absorption of orally administered drugs. Consequently, these postures favour a shorter time to reach peak plasma drug concentration (t max ) and a higher maximum plasma drug concentration (C max ) and-in the case of transient saturation of first-pass metabolism-total exposure (area under the concentration-time curve, AUC) in comparison to recumbent left and supine positions (e.g. nifedipine: AUC 30 and 38% higher in standing and right lateral position vs. left lateral position; C max 149 and 80% higher, respectively). The magnitude of these postural effects depends strongly on the nature and amount of liquids and food ingested before drug administration and is most pronounced in the fasting state and after administration with a nonnutrient liquid. Changes in splanchnic-hepatic blood flow (e.g. reduction of estimated hepatic perfusion by 37% in standing vs. supine position) may substantially affect the metabolism of orally administered drugs, especially of those with a high/saturable first-pass metabolism. For highly protein-bound drugs (e.g. phenytoin, imipramine), the total plasma concentration has been found to be approximately 10% higher in standing than lying subjects due to changes in plasma volume. Conclusions Positioning of a patient may be an effective method of enhancing or retarding absorption of some drugs in appropriate clinical situations (e.g. toxic ingestions, bedridden patients). In clinical pharmacokinetic trials, such as bioequivalence studies, defining and maintaining posture precisely is a useful approach for reducing within-and between-subject variability.Keywords Absorption . Gastric emptying . Pharmacokinetics . Posture IntroductionThe influence of body position on physiological characteristics and pharmacokinetics has been investigated for several decades. The first study on this topic (effects of posture on gastric emptying) was reported to have been performed as early as 1918 [1] when it was observed that barium was emptied faster when subjects lay on the right side compared to other positions. Since then, a multitude of studies has addressed various aspects of postural effects, especially those on gastrointestinal motility, haematological parameters/perfusion and the pharmacokinetics of orally administered drugs.

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Section: Effects Of Posture On the Gastric Residence Time Of Fluids Amentioning

confidence: 99%

Influence of posture on pharmacokinetics

Queckenberg

Fuhr

2008

Eur J Clin Pharmacol

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“…Further decrease in rate of release of the drug with increase in pH of the dissolution media is in agreement with its solubility profile. Such changes in the dissolution profiles of the drug within the expected pH range of the stomach was anticipated to be one cause of high individual variability during in vivo release of the drug among individuals since the pH of the stomach is known to differ significantly among individuals 17) and is within the range of 1 to 3 18) or even higher, 1 to 5 19) under fasting conditions. Furthermore, the very slow dissolution rate in the FaSSIF suggests that if undissolved loratadine is emptied from the stomach, the absorption rate will be dramatically slower compared with those individuals where complete dissolution occurs in the stomach.…”

Section: Discussionmentioning

confidence: 99%

“…The gastric emptying rate, therefore, can vary according to the phase of the GI motility at the time the drug was taken. 19) During the in vitro studies, the stirring rate had a pronounced effect on the extent and variability of the dissolution (Figs. 2A, 2B) further suggesting that differences in GI motility conditions among individuals may be contributing to the variability in the bioavailability data.…”

Section: Discussionmentioning

confidence: 99%

Classification of Loratadine Based on the Biopharmaceutics Drug Classification Concept and Possible in Vitro-in Vivo Correlation

Khan

Raušl

Zanoski

et al. 2004

Biological & Pharmaceutical Bulletin

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Loratadine, chemically known as ethyl 4-(8-chloro-5,6-dihydro-11H-benzo [5,6]-cyclohepta[1,2-b]pyridin-11-ylidene)-1-piperidinecarboxylate, is a weak base with a pK a value of ca. 6 (calculated in our laboratories). It is absorbed rapidly following oral administration in humans giving maximum plasma concentration (C max ) in about 1-1.5 h when administered under fasting conditions, but the degree of inter-subject variability in the pharmacokinetic parameters was reported to be very high. The C max and plasma concentration-time (AUC t ) data obtained following oral administration of 10 mg, 20 mg, and 40 mg loratadine capsules were found to have a dose-proportional relationship. 3)Following oral dosing 80% of the total dose administered was found equally distributed between urine and faeces in the form of metabolic products within 10 d.4) The kinetics of loratadine observed during a multiple dose study were found comparable to those reported from single dose studies, but the mean plasma concentration-time data were approximately 90% greater than that reported for single dose data, and the steady state plasma concentrations were apparent by the fifth day of dosing. 5)The objective of the studies reported here was two fold; firstly, to classify loratadine according to the biopharmaceutics drug classification scheme, 6,7) and secondly, to compare plasma time profiles predicted from in vitro dissolution data with experimental plasma time data in order to select the most appropriate conditions for in vitro assessment of loratadine solid dosage forms. Furthermore, attempts have been made to investigate factors responsible for the high inter-subject variability in pharmacokinetic parameters of the drug. MATERIALS AND METHODS MaterialsLoratadine of European Pharmacopoeia (EP) quality was purchased from Chemo Iberica S.A. (Lugano, Switzerland). Standard pharmacopoeial grade excipients were used in the tablet formulation. Egg lecithin used for dissolution studies under biorelevant conditions was a gift from Lipoid AG (Cham, Switzerland). Crude sodium taurocholate (batch no. 386645/1, standardised against a lot of the pure substance containing above 97%) was purchased from Sigma Chemical Co. (St. Louis, U.S.A.). Sodium lauryl sulphate, hydrochloric acid and all other chemicals used for evaluation of the tablets were of analytical grade. The tablets were prepared in-house (by wet granulation technology using starch paste as a binder).For permeability testing, Caco-2 cells were obtained from the European Collection of Cell Cultures (U.K.) at passage 20. Dulbecco's Eagles medium (DMEM) containing glucose (4500 mg/ml) was purchased from Imunološki Zavod, Zagreb (Croatia). Fetal bovine serum (FBS), glutamax I, nonessential amino acids (NEAA), penicillin/streptomycin, fungizone and 0.25% trypsin-EDTA were obtained from Gibco, Life Technologies (U.K.). Hanks balanced salt solution (HBSS) and dimethylsulphoxide (DMSO) were purchased from Sigma-Aldrich (Germany). Tert-butyl methyl ether (TBME) was supplied by Merck (Germany).Solubili...

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“…These MMC last about 2-3 h in total, but are divided into 4 phases, of which Phase 3 results in the strongest contractions but lasts only about 15 min [so-called 'housekeeper waves'; (13)]. Non-nutrient liquids, particularly larger volumes (>250 ml), are moved quickly from the stomach throughout the MMC, but solids are only moved into the small intestine during the brief Phase 3.…”

Section: Food and Gastrointestinal Physiologymentioning

confidence: 99%

Pharmacokinetic studies in healthy volunteers in the context of in vitro/in vivo correlations

Oosterhuis¹,

Jonkman²

1993

Eur. J. Drug Metab. Pharmacokinet.

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A multitude of in vivo variables can influence systemic drug absorption after intake of an oral formulation. For the measurement of consistent in vivo parameters within and between pharmacokinetic studies it is of primary importance that such variables be recognized. Consequently, as many variables as possible should be eliminated or controlled by proper study designs to prevent (or minimize) their disturbance of in vitro/in vivo correlations. The possible influences of some important variables are elaborated and discussed in this paper. The influences of food can be anticipated and controlled against the background of gastrointestinal physiology with and without food and its interplay with the dosage form. Food, and also posture and exercise, may influence splanchnic-hepatic blood flow which may substantially affect the absorption of drugs with a high first-pass metabolism. The influence of the discussed variables may be modified by the dosage form of a particular drug. Single dose studies are appropriate for studying immediate release formulations and in the development of controlled release formulations. Multiple dose studies are preferred for the formal validation of controlled release formulations.

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Physiologic considerations in drug absorption from the gastrointestinal tract

Cited by 50 publications

References 24 publications

Influence of posture on pharmacokinetics

Influence of posture on pharmacokinetics

Classification of Loratadine Based on the Biopharmaceutics Drug Classification Concept and Possible in Vitro-in Vivo Correlation

Pharmacokinetic studies in healthy volunteers in the context of in vitro/in vivo correlations

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