Estimation of Oral Bioavailability in the Rat by the Accelerated Infusion Technique

Guo, Zijian; Luo, Youfu; Dobson, Glenn L.; Marietta, M.; Rhodes, Gerald R.; Hidalgo, Ismael J.

doi:10.1211/0022357001774840

Cited by 3 publications

(5 citation statements)

References 8 publications

(14 reference statements)

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“…[41], after oral administration of 30 and 150 mg/kg doses, obtained an elimination constant rate ranging from 0.26 to 2.45/h. To compare the apparent volume of distribution obtained in the current study and published values of volume of distribution, the bioavailability of acetaminophen by the oral route (F = 90% [36,37]) was taken into account. The population pharmacokinetic parameters were calculated taking into account the inter‐individual variability while the published data used above to make the comparison were means of individual values.…”

Section: Discussionmentioning

confidence: 99%

“…The high variability in the data reported by Cintron because of an heterogeneous experimentation (five crewmembers on three different flights) was a limiting factor for comparing the data reported here. With respect to the intestinal absorption rate, acetaminophen is totally ( F = 80–90% [36,37]) and rapidly absorbed ( t max = 12–15 min) [34,35] through the intestinal wall by a passive diffusion [28]. For drugs with a passive diffusion, the rate of diffusion depends on the gradient of concentrations between the intestinal lumen and the intestinal blood flow [25].…”

Section: Discussionmentioning

confidence: 99%

“…This parameter depends on all the events that control the arrival into the central compartment, in particular the gastric emptying rate and the intestinal absorption rate. In the case of acetaminophen, there is a significant correlation between the Ka and the gastric emptying rate determined by a scintigraphic method [32,33] because acetaminophen is totally and rapidly absorbed through the intestinal wall [34–37]. Kel is the first‐order rate constant of elimination of drug from the body.…”

Section: Pharmacokinetic and Statistical Analysismentioning

confidence: 99%

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Influence of simulated weightlessness on the pharmacokinetics of acetaminophen administered by the oral route: a study in the rat

Gandia¹,

Saivin²,

Lavit³

et al. 2004

Fundamemntal Clinical Pharma

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During space flights, the human body is submitted to weightlessness which induces physiological variations that could modify drug disposition during space missions. Since space experiments are infrequent and difficult to perform, in order to evaluate pharmacokinetic modifications, simulation experiments of weightlessness have to be carried out on earth, using animal-models such as the Morey-Holton model. In this model, rats are suspended by the tail with their front paws on the ground. We studied the effects of simulated weightlessness on drug absorption and on gastric emptying, using acetaminophen as a probe. Three periods of suspension (1, 2 and 5 days) were compared with two control groups (free and attached rats). The attached group was used to evaluate a possible 'stress effect' caused by the suspension device. Each group was composed of 36 rats (12 sampling times and three rats per time). An oral dose of acetaminophen (100 mg/kg) was administered and blood samples were collected before and up to 12 h after administration. Plasma assays were performed using an high-performance liquid chromatography method with UV detection. The calculated population pharmacokinetic parameters were Ka, Kel (first order absorption and elimination constants) and Vd/F (apparent volume of distribution). The statistical interpretation of the population pharmacokinetic parameters indicated that 2 days of suspension significantly decreased the Vd/F by 83% and the Ka by 125%. The increase in the Ka was probably because of an increased acceleration of the gastric emptying and/or to a decrease in the total peripheral resistance which increased intestinal blood flow.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Pharmacokinetic and Statistical Analysismentioning

confidence: 99%

See 1 more Smart Citation

Influence of simulated weightlessness on the pharmacokinetics of acetaminophen administered by the oral route: a study in the rat

Gandia¹,

Saivin²,

Lavit³

et al. 2004

Fundamemntal Clinical Pharma

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“…Given the diversity of the meals ingested every day, it is impossible to determinate exactly the time necessary for a drug to pass through the pylorus and this phenomenon could be considered as a random event [60]. acetaminophen is totally (F ¼ 80-90%) [70,71] and rapidly absorbed (t max ¼ 12-19 min) [33,72] through the intestinal wall by passive diffusion [73], and so consequently its absorption profile depends directly on the rate of gastric emptying. acetaminophen is totally (F ¼ 80-90%) [70,71] and rapidly absorbed (t max ¼ 12-19 min) [33,72] through the intestinal wall by passive diffusion [73], and so consequently its absorption profile depends directly on the rate of gastric emptying.…”

Section: Animal Modelsmentioning

confidence: 99%

“…To study the influence of simulated weightlessness on gastric emptying, we chose acetaminophen as a probe [27,[61][62][63][64][65][66][67][68][69]. acetaminophen is totally (F ¼ 80-90%) [70,71] and rapidly absorbed (t max ¼ 12-19 min) [33,72] through the intestinal wall by passive diffusion [73], and so consequently its absorption profile depends directly on the rate of gastric emptying. Three periods of suspension (1, 2 and 5 days) were compared with two control groups (free and attached rats).…”

Section: Animal Modelsmentioning

confidence: 99%

The influence of weightlessness on pharmacokinetics

Gandia

Saivin

Houin

2005

Fundamemntal Clinical Pharma

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The primary hostile factor during a spaceflight is the lack of gravity, which can induce space motion sickness and act on bones, muscles and the cardiovascular system. These physiological effects may modify the pharmacokinetics of the drugs administered during the flight producing reduced pharmacological activity or appearance of adverse effects. Given the small number of spaceflights and the difficulties of conducting experiments during missions, pharmacokinetic data obtained in flight are insufficient to determine if drug monitoring is necessary for the drugs present in the onboard medical kit. Therefore, validated earthbound models like tail-suspension performed with animals and long-term bedrest performed with human volunteers are used to simulate weightlessness and to study the pharmacokinetic variations of either absorption, distribution, or elimination of drugs. As a result of these studies, it is possible to make some dosing recommendations but more information is necessary to predict with precision all of the pharmacokinetic variations occurring in spaceflight. To collect more pharmacokinetic information, head-down bedrest studies are still the best solution and as saliva is an appropriate substitution for plasma for some drugs, salivary sampling can be planned during flights.

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Design and Characterization of Nanocrystals of Lovastatin for Solubility and Dissolution Enhancement

Nanjwade¹,

Derkar²,

Bechra³

et al. 2011

J Nanomedic Nanotechnol

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A major hurdle in pharmaceutical formulation is water insolubility of most of the drugs affecting stability and bioavailability of the drug, if the drug is also insoluble in organic medium, it is difficult to deliver the drug in a sufficiently bioavailable form and hence it is a great challenge to formulation researchers to overcome such difficulty. Although some approaches are available for enhancing the dissolution of poorly soluble drugs but has certain draw backs like low drug loading and large doses. However, a new solution to poorly water soluble drug candidates is now available i.e. nanonisation and it leads to much more soluble, more biologically available and safer dosage form of poorly soluble and poorly bioavailable drugs. In the present work, a nanocrystal of lovastatin was formulated by using simple precipitation method without using stabilizer or surfactant and it was found that formulation at 3 mM concentration of drug with the acetone and methanol as a solvent and at proper dilution (50 times) of drug solution with water, nanocrystals with less particle size is possible with slight change in crystallinity. It has also shown that, the drug has enhanced saturation solubility, increased dissolution rate and more bioavailable in biological fluid when drug formulated by using acetone and methanol as a solvent. Whereas drug formulation with acetonitrile has large particle size, less saturation solubility and low rate of dissolution.

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Estimation of Oral Bioavailability in the Rat by the Accelerated Infusion Technique

Cited by 3 publications

References 8 publications

Influence of simulated weightlessness on the pharmacokinetics of acetaminophen administered by the oral route: a study in the rat

Influence of simulated weightlessness on the pharmacokinetics of acetaminophen administered by the oral route: a study in the rat

The influence of weightlessness on pharmacokinetics

Design and Characterization of Nanocrystals of Lovastatin for Solubility and Dissolution Enhancement

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