Abstract：
BACKGROUND:Experimental determination of a drug's oral bioavailability in humans is cost and time consuming; therefore, is usually performed on preclinical animals. It is believed that animal data are predictive of human data; however, there are some doubts regarding the reliability of this concept. The aim of this study is to clarify whether it is possible to predict a correlation between human and animal bioavailability data based on structural parameters. METHODS:Oral bioavailability data of drugs for humans and preclinical animals (rats and dogs) were collected from the literature. Structural descriptors [Abraham solvation parameters, topological polar surface area (TPSA), logarithm of partition coefficient (logP) and logarithm of distribution coefficient at pH = 6.8 (logD6.8)] were calculated by ACD/Labs software. Data were divided into two classes by percentage deviation (PD) of oral bioavailability between humans and preclinical animals (PD < 40%: class I and PD > 40%: class II). Classification-based models were used to predict the class of each drug using structural parameters. RESULTS:The results of this study revealed that logD6.8 is the main parameter for evaluation of the correlation between oral bioavailability in humans and animals. Moreover, the developed models using logistic regression based on logP, TPSA and Abraham solvation parameters are able to predict the class of a drug with 75% accuracy. CONCLUSION:The structural parameters and developed models in this study can be used to find compounds that have an acceptable correlation between oral bioavailabilities in animals, i.e., rats and dogs, and humans.
journal_name
Eur J Drug Metab Pharmacokinetjournal_title
European journal of drug metabolism and pharmacokineticsauthors
Beheshti S,Shayanfar Adoi
10.1007/s13318-020-00636-2subject
Has Abstractpub_date
2020-12-01 00:00:00pages
771-783issue
6eissn
0378-7966issn
2107-0180pii
10.1007/s13318-020-00636-2journal_volume
45pub_type
杂志文章abstract：:Parenteral phenytoin solution (Dilantin) was given rectally three times a day for three days to two beagle dogs. This was well tolerated, with no evidence of mucosal irritation noted either on endoscopic nor on rectal mucosal biopsy. When given in this manner, phenytoin is absorbed to a limited degree in canines. Pare...
journal_title：European journal of drug metabolism and pharmacokinetics
pub_type： 杂志文章
doi：10.1007/BF03190088
更新日期：1988-10-01 00:00:00
abstract：:Following i.v. administration of mono-HR to the beagle, plasma levels of both mono-HR and its glucuronide conjugates fell rapidly, neither being detectable 8 h after injection. Following oral administration of 14C-mono-HR, mono-HR-glucuronide was detected in plasma, confirming the absorption of mono-HR, and low levels...
journal_title：European journal of drug metabolism and pharmacokinetics
pub_type： 杂志文章
doi：10.1007/BF03189428
更新日期：1979-01-01 00:00:00
abstract：:Sertraline potently inhibits cytochrome P450 2B6 (CYP2B6) in vitro. Bupropion is commonly co-prescribed with sertraline and is exclusively metabolized by CYP2B6 to its major active metabolite hydroxybupropion. Putatively the co-administration of bupropion and sertraline could lead to a significant pharmacokinetic drug...
journal_title：European journal of drug metabolism and pharmacokinetics
pub_type： 杂志文章
doi：10.1007/s13318-011-0065-6
更新日期：2012-03-01 00:00:00
abstract：:The pharmacokinetics of midazolam and of its main metabolite, 1-hydroxymidazolam, were investigated in intensive care patients after intravenous bolus of 0.2 mg/kg followed by a 0.1 mg/kg/h intravenous infusion of midazolam over 2 hours. A wide interpatient variability of the main pharmacokinetic parameters of midazol...
journal_title：European journal of drug metabolism and pharmacokinetics
pub_type： 杂志文章
doi：10.1007/BF03189348
更新日期：1998-04-01 00:00:00
abstract：:We studied the pharmacokinetics of moguisteine, a racemic non-narcotic peripheral antitussive drug, in 12 healthy male subjects after a single oral administration of 200 mg. The unchanged drug was absent in plasma and urine of all subjects. Moguisteine was immediately and completely hydrolyzed to its main active metab...
journal_title：European journal of drug metabolism and pharmacokinetics
pub_type： 杂志文章
doi：10.1007/BF03190242
更新日期：1995-10-01 00:00:00
abstract：:A generic drug product (test product) is bioequivalent to an innovator product (reference product) when their bioavailabilities in the same molar dose are similar. Bioavailability is expressed by pharmacokinetic parameters such as the area under plasma concentration-time curve (AUC), the maximum plasma concentration (...
journal_title：European journal of drug metabolism and pharmacokinetics
pub_type： 杂志文章
doi：10.1007/BF03226406
更新日期：2005-01-01 00:00:00
abstract：:A remarkably large species difference in cinchonidine oxidation activity catalyzed by aldehyde oxidase (AO) has been known, in particular between rabbit and monkey. As the first step in clarifying the phenomenon from the view point of structures of the active site, we attempted to construct an expression system of rab...
journal_title：European journal of drug metabolism and pharmacokinetics
pub_type： 杂志文章
doi：10.1007/BF03191175
更新日期：2009-07-01 00:00:00
abstract：:Thymoquinone (THQ), the active constituent of Nigella sativa seeds, has demonstrated some potential pharmacological activities. The present study was designed to investigate the pharmacokinetic behavior of THQ following intravenous (IV) and oral (PO) administration using an animal model. THQ was given vascularly (5 mg...
journal_title：European journal of drug metabolism and pharmacokinetics
pub_type： 杂志文章
doi：10.1007/s13318-014-0207-8
更新日期：2015-09-01 00:00:00
abstract：BACKGROUND AND OBJECTIVE:The antitumor activity and toxicity of doxorubicin are potentiated and attenuated by calcitriol, respectively. Potentially, calcitriol can be combined with doxorubicin for clinical benefit in chemotherapy. To gain insight into the interaction between doxorubicin and calcitriol, proposed for com...
journal_title：European journal of drug metabolism and pharmacokinetics
pub_type： 杂志文章
doi：10.1007/s13318-020-00632-6
更新日期：2020-10-01 00:00:00
abstract：:Diabetes mellitus is becoming an increasingly prevalent disease that concerns patients and healthcare professionals worldwide. Among many anti-diabetic agents in clinical uses, numerous reports are available on their altered pharmacokinetics because of changes in the expression of drug transporters and metabolic enzym...
journal_title：European journal of drug metabolism and pharmacokinetics
pub_type： 杂志文章,评审
doi：10.1007/s13318-015-0306-1
更新日期：2016-06-01 00:00:00
abstract：:The evaluation of new intranasal medications requires the development of in vitro cell model suitable for high-throughput screening studies. The aim of a pharmacological model is to closely mimic the barrier properties of human nasal mucosa that will influence drug pharmacokinetics. In this context, the human nasal ce...
journal_title：European journal of drug metabolism and pharmacokinetics
pub_type： 杂志文章,评审
doi：10.1007/s13318-017-0426-x
更新日期：2018-02-01 00:00:00
abstract：:Permeability coefficients of seven compounds belonging to a true homologous series (4-alkylanilines) through several different synthetic and biological membranes were assayed in a two-chamber diffusion cell. Permeability-lipophilicity relationships for the experimental data were established and compared in order to as...
journal_title：European journal of drug metabolism and pharmacokinetics
pub_type： 杂志文章
doi：
更新日期：1991-01-01 00:00:00
abstract：:The pharmacokinetic-pharmacodynamic (PK-PD) relationship of the proton pump inhibitor rabeprazole in healthy Chinese volunteers was characterized via a population approach. Healthy Chinese male volunteers were enrolled in the clinical trial. Subjects were divided into three groups by their CYP2C19 genotype. Serum conc...
journal_title：European journal of drug metabolism and pharmacokinetics
pub_type： 杂志文章
doi：10.1007/BF03190639
更新日期：2006-01-01 00:00:00
abstract：:The effects of potassium ethylxanthogenate (PEX) and 2,3-Dimercaptopropane sulphonate sodium (Unithiol) on the pentobarbital (40 mg/kg, body weight i.v.) (PB) sleeping time, pharmacokinetics, and metabolism, were studied in comparative experiments on male albino mice. It was established that the pretreatment of animal...
journal_title：European journal of drug metabolism and pharmacokinetics
pub_type： 杂志文章
doi：10.1007/BF03189539
更新日期：1982-01-01 00:00:00
abstract：:The pharmacokinetics of chlordemethyldiazepam--a pharmacologically very active new 1,4-benzodiazepine derivative--in healthy subjects after administration of a single oral dose of 2 mg, was studied. Peak concentrations were reached in 1.2 +/- 0.2 hours. Plasma levels declined with a biphasic pattern, and the eliminati...
journal_title：European journal of drug metabolism and pharmacokinetics
pub_type： 杂志文章
doi：10.1007/BF03189844
更新日期：1986-07-01 00:00:00
abstract：:The kinetics of fenfluramine isomers were studied in the rat following oral doses of racemic fenfluramine. The data, analyzed using an analogue computer, indicate that the d-fenfluramine is metabolised and excreted at a slower rate than the 1-isomer, resulting in higher plasma and brain concentrations. The kinetic par...
journal_title：European journal of drug metabolism and pharmacokinetics
pub_type： 杂志文章
doi：10.1007/BF03189529
更新日期：1981-01-01 00:00:00
abstract：:This study examined the effects of the absorption enhancers, acylcarnitines, on efflux transporting systems, including P-glycoprotein (P-gp) and other efflux transporters, and elucidated the importance of acyl chain length and the concentration of acylcarnitine on the activity of efflux transport. The effects of two a...
journal_title：European journal of drug metabolism and pharmacokinetics
pub_type： 杂志文章
doi：10.1007/s13318-010-0001-1
更新日期：2010-09-01 00:00:00
abstract：BACKGROUND AND OBJECTIVES:Gadobenate dimeglumine (Gd-BOPTA) is a commercialised hepatobiliary contrast agent used during liver magnetic resonance imaging (MRI) to detect liver diseases. It enters into human hepatocytes through organic anion transporting polypeptides (OATP1B1/B3) and crosses the canalicular transporter ...
journal_title：European journal of drug metabolism and pharmacokinetics
pub_type： 杂志文章
doi：10.1007/s13318-016-0382-x
更新日期：2017-08-01 00:00:00
abstract：:Hepatic distributional volumes were investigated in the in situ perfused rat liver. Perfusion experiments were conducted using Krebs bicarbonate buffer delivered via the portal vein in single-pass mode at a total flow rate of 15 mL/min. A bolus dose of normal erythrocytes (RBC, vascular marker) and Evans blue (EB, ext...
journal_title：European journal of drug metabolism and pharmacokinetics
pub_type： 杂志文章
doi：10.1007/BF03190469
更新日期：2006-10-01 00:00:00
abstract：BACKGROUND AND OBJECTIVES:In the present work, pharmacological and pharmacokinetic properties of the supramolecular complex of non-steroid anti-inflammatory drug ibuprofen (IBU) with natural polysaccharide arabinogalactan (AG) were studied. The main goals of such complexation were the increase of ibuprofen's bioavailab...
journal_title：European journal of drug metabolism and pharmacokinetics
pub_type： 杂志文章
doi：10.1007/s13318-016-0357-y
更新日期：2017-06-01 00:00:00
abstract：:Tectorigenin (Te) is a main active component in the flowers of Pueraria thomsonii Benth. and the rhizomes of Belamcanda chinensis (L.) DC. Previously, we have reported the pharmacokinetic properties of Te in rat plasma. The purpose of this study was to investigate the urinary excretion of Te after oral administration ...
journal_title：European journal of drug metabolism and pharmacokinetics
pub_type： 杂志文章
doi：10.1007/s13318-014-0202-0
更新日期：2015-09-01 00:00:00
abstract：:Monoclonal antibodies are capable of modulating drug metabolising enzymes resulting in unexpected plasma concentrations of a drug when given concomitantly. Therefore plasma concentration of paclitaxel (PTX) and its metabolites has been monitored in 10 patients with advanced breast cancer during treatment with PTX alon...
journal_title：European journal of drug metabolism and pharmacokinetics
pub_type： 杂志文章
doi：10.1007/BF03190613
更新日期：2005-07-01 00:00:00
abstract：:The hypoxic cell radiosensitizing drug, misonidazole (Miso) (Ro 07-0582) and its demethylated metabolite were administered to Wistar rats at different dose levels to examine their renal elimination. The data were consistent with a model in which Miso is eliminated mainly after biotransformation into desmethylmisonidaz...
journal_title：European journal of drug metabolism and pharmacokinetics
pub_type： 杂志文章
doi：10.1007/BF03189740
更新日期：1985-07-01 00:00:00
abstract：:Hepatic clearance of gitoxin has been studied in the rabbit and compared with that of digoxin using an isolated perfused liver technique. During 1.5 hour perfusions with a modified Krebs-Henseleit solution, gitoxin perfusate levels decreased biexponentially; the distribution and elimination half-lives were estimated t...
journal_title：European journal of drug metabolism and pharmacokinetics
pub_type： 杂志文章
doi：10.1007/BF03189574
更新日期：1983-01-01 00:00:00
abstract：:The cardioselective beta-adrenergic blocking drug Visacor (ICI 141,292) was dosed to six beagle dogs in a randomized cross-over manner. Five formulations were examined i.e. a 15 mg/kg intravenous solution, a 50 mg/kg oral solution, and 50, 100 and 200 mg/kg oral powder formulations. Whole blood and urine samples were ...
journal_title：European journal of drug metabolism and pharmacokinetics
pub_type： 杂志文章
doi：10.1007/BF03189616
更新日期：1984-04-01 00:00:00
abstract：:Cytochrome P450 from rat brain mitochondrial and microsomal fractions was found to be inducible by 3-methylcholanthrene, both in quantity of enzyme and in activity towards 7-ethoxyresorufin, which is a model substrate for the cytochrome P450 isoform specifically induced by 3-methylcholanthrene. Conversely, a phenobarb...
journal_title：European journal of drug metabolism and pharmacokinetics
pub_type： 杂志文章
doi：10.1007/BF03189910
更新日期：1987-10-01 00:00:00
abstract：:A bioequivalence study compares the bioavailability between a test and a reference drug product in terms of the rate and extent of drug absorption. Area under the plasma concentration-time curve (AUC) and maximum plasma concentration (Cmax) are the pharmacokinetic parameters that serve as characteristics for the asses...
journal_title：European journal of drug metabolism and pharmacokinetics
pub_type： 杂志文章
doi：10.1007/BF03190024
更新日期：1999-07-01 00:00:00
abstract：:The metabolism of (-)-(S)-nicotine has been investigated following intratracheal administration to the recirculating perfused rabbit lung model. The metabolic products present in the perfusate were identified by co-chromatography (HPLC and GC) with authentic standards and quantified by HPLC. After the 180 min perfusio...
journal_title：European journal of drug metabolism and pharmacokinetics
pub_type： 杂志文章
doi：10.1007/BF03190976
更新日期：1997-10-01 00:00:00
abstract：:The disposition of RS-tocainide in three healthy volunteers has been studied after oral administration of a pseudoracemic mixture containing S(+) [3H] tocainide as a radioactive tracer together with a therapeutic dose of the racemate. Analytical methods based on HPLC have been developed to measure S(+) and R(-) tocain...
journal_title：European journal of drug metabolism and pharmacokinetics
pub_type： 杂志文章
doi：10.1007/BF03189644
更新日期：1984-07-01 00:00:00
abstract：:The aim of this work was to study the influence of labelling on caffeine metabolism according to the incubation mode. It has been observed that labelling induces an isotopic effect on metabolisation speed: apparent half-lives are systematically increased. Moreover, isotopic effects are in agreement with those previous...
journal_title：European journal of drug metabolism and pharmacokinetics
pub_type： 杂志文章
doi：10.1007/BF03189795
更新日期：1997-04-01 00:00:00
