Biopharmaceutics as a Basis for the Design of Drug Products

Benet, Leslie Z.

doi:10.1016/b978-0-12-060304-6.50007-1

Cited by 9 publications

(3 citation statements)

References 53 publications

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“…As NTZ and its active metabolite, T, are insoluble in water (Prod Info Alinia, 2005), the amount of drug initially available for absorption by controlling its release to the gastrointestinal fluids was reduced, and consequently the rate of appearance of the drug in the small intestine was decreased. This latter site is regarded normally as the optimum site of absorption for most drugs even if the drugs are readily absorbed from the stomach (Levy, 1961), and even if the drug is ionized in the intestine and nonionized in the stomach (Benet, 1973). The rate of absorption of T could also be affected by the fact that goats are small ruminants and have their own physiological features.…”

Section: Discussionmentioning

confidence: 99%

The pharmacokinetics of nitazoxanide active metabolite (tizoxanide) in goats and its protein binding abilityin vitro

Xue

ZHANG

et al. 2010

Journal of Veterinary Pharmacology and Therapeutics

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The pharmacokinetics of tizoxanide (T), the active metabolite of nitazoxanide (NTZ), and its protein binding ability in goat plasma and in the solutions of albumin and alpha-1-acid-glycoprotein were investigated. The plasma and protein binding samples were analyzed using a high-performance liquid chromatography (HPLC) assay with UV detection at 360 nm. The plasma concentration of T was detectable in goats up to 24 h. Plasma concentrations vs. time data of T after 200 mg/kg oral administration of NTZ in goats were adequately described by one-compartment open model with first order absorption. As to free T, the values of t(1/2Ka), t(1/2Ke), T(max), C(max), AUC, V/F((c)), and Cl((s)) were 2.51 +/- 0.41 h, 3.47 +/- 0.32 h, 4.90 +/- 0.13 h, 2.56 +/- 0.25 microg/mL, 27.40 +/- 1.54 (microg/mL) x h, 30.17 +/- 2.17 L/kg, and 7.34 +/- 1.21 L/(kg x h), respectively. After beta-glucuronidase hydrolysis to obtain total T, t(1/2ke), C(max), T(max), AUC increased, while the V/F((c)) and Cl((s)) decreased. Study of the protein binding ability showed that T with 4 microg/mL concentration in goat plasma and in the albumin solution achieved a protein binding percentage of more than 95%, while in the solution of alpha-1-acid-glycoprotein, the percentage was only about 49%. This result suggested that T might have much more potent binding ability with albumin than with alpha-1-acid-glycoprotein, resulting from its acidic property.

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Section: Discussionmentioning

confidence: 99%

The pharmacokinetics of nitazoxanide active metabolite (tizoxanide) in goats and its protein binding abilityin vitro

Xue

ZHANG

et al. 2010

Journal of Veterinary Pharmacology and Therapeutics

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“…The numerator CD represents the driving force of the absorptive process, namely the intestinal concentration of the diffusing moiety. It is determined by pharmaceutical factors, such as disintegration and dissolution characteristics, and by physiological factors, such as gastrointestinal motility and pH, intestinal secretion and intestinal flora, and concomitant intake of food, fluids, or interfering drugs (Bates and Gibaldi, 1970;Benet, 1973;Prescott, 1974).…”

Section: Pathophysiology Of Cardiac Failurementioning

confidence: 99%

Pharmacokinetics in Patients with Cardiac Failure

Benowitz

Meister

1976

Clinical Pharmacokinetics

131

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Cardiac failure is often associated with disturbances in cardiac output, autonomic nervous system activity, central and systemic venous pressures, and sodium and water metabolism. These disturbances influence the extent and pattern of tissue perfusion, may lead to tissue hypoxia and visceral congestion, and may alter gastrointestinal motility. By these mechanisms, cardiac failure potentially affects absorption and disposition characteristics of drugs, which may necessitate adjustment in dosage regimen for optimum therapy. Lignocaine is the drug which has been studied most extensively in cardiac failure. Volumes of distribution and clearance are decreased. As a drug whose metabolism is largely limited by liver blood flow, decreased blood flow to the liver accounts for some of the change in clearance, but impaired hepatic metabolism appears also to play a role in some patients. Accumulation of active metabolites of lignocaine and procainamide in patients with cardiac failure can influence therapeutic and toxic effects. Theophylline metabolism, which is largely independent of blood flow, appears to be reduced significantly in patients with severe cardiac failure and necessitates reduction of dosage. In the presence of severe cardiac failure, digoxin clearance may be less than anticipated on the basis of estimates of renal function. Quinidine plasma levels may be higher after single doses due to reduced volume of distribution. Quinidine metabolites are believed not to be pharmacologically active but may create confusion with nonspecific assays. Specific assays are recommended in cardiac failure, especially complicated by renal insufficiency. Data are lacking relating pharmacokinetic alterations to haemodynamic measurements in patients with cardiac failure. Whereas the direction of change in pharmacokinetic parameters may be predicted, variability in the magnitude of change is so great that determination of drug concentration in blood remains as essential adjunct to therapy.

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“…"Biopharmaceutics, the science of input", is how Leslie Benet described this branch of science some years ago (1973) [1]. This is the simplest and, in my opinion, one of the best definitions that has been made of this relatively recent field, which first became included in the pharmaceutical studies curriculum in the 1960s following a paper by G. Levy, published in 1961 in the Journal of Pharmaceutical Sciences, in which the term "biopharmaceutics" was officially used for the first time [2].…”

Section: Discussionmentioning

confidence: 99%

An overview about Biopharmaceutics in Europe

Aiache

2005

Eur. J. Drug Metab. Pharmacokinet.

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In Europe, the concept of biopharmaceutics was first introduced at the end of the 70s by various highly informed young Europeans who took into full account the publications and studies carried out by the first generation of explorers in this area in the United States such as John Wagner, Gerhard Levy, and W.A. Ritschel, amongst others. Their primary aim was to develop bioavailability studies for the registration of generics or new dosage forms. They then worked on setting up a new system for drug dissolution in vitro, including in vitro and in vivo correlations to better define the formulations. All this research led to the publication of numerous reports on different congresses, the most important of these being the European Congress of Biopharmaceutics and Pharmacokinetics, which is held once every two years in a European country and includes a large number of participants with an attendance ranging from 300 to 500 persons. During this same period, books were published in French and other European languages such as English, German and Spanish, with the result that updated information was efficiently circulated throughout all European countries. In the near future, the introduction of the biopharmaceutical classification as well as new in vitro models will certainly make a positive contribution to the further development of research in this area.

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Biopharmaceutics as a Basis for the Design of Drug Products

Cited by 9 publications

References 53 publications

The pharmacokinetics of nitazoxanide active metabolite (tizoxanide) in goats and its protein binding abilityin vitro

The pharmacokinetics of nitazoxanide active metabolite (tizoxanide) in goats and its protein binding abilityin vitro

Pharmacokinetics in Patients with Cardiac Failure

An overview about Biopharmaceutics in Europe

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