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International Journal of Pharmaceutics Feb 2009A database of human dermatopharmacokinetic parameters of 12 transdermal patches is established. The effect of system design, application site, and metabolism on... (Review)
Review
A database of human dermatopharmacokinetic parameters of 12 transdermal patches is established. The effect of system design, application site, and metabolism on pharmacokinetic data is discussed, and interindividual variability of data and its possible sources evaluated. Using multiple regression analysis, two equations based on drugs physicochemical characteristics are suggested for partial prediction of peak plasma concentration (C(max)) after patch application. Patch application presumably decreases variance as rub-off, wash and exfoliation steps are diminished. The results showed that interindividual variation, in terms of coefficient of variation (CV) of C(max), is inversely correlated with drugs molecular weight and lipophilicity in the range of 200
Topics: Administration, Cutaneous; Biological Availability; Dose-Response Relationship, Drug; Humans; Pharmaceutical Preparations; Pharmacokinetics; Predictive Value of Tests; Regression Analysis; Skin Absorption; Therapeutic Equivalency
PubMed: 19100821
DOI: 10.1016/j.ijpharm.2008.11.020 -
Clinical Pharmacology in Drug... Sep 2022This study aimed to evaluate the bioequivalence of two pazopanib tablet formulations in healthy Chinese subjects. A randomized, open-label, single-dose, two-period,... (Randomized Controlled Trial)
Randomized Controlled Trial
This study aimed to evaluate the bioequivalence of two pazopanib tablet formulations in healthy Chinese subjects. A randomized, open-label, single-dose, two-period, two-sequence, crossover study was conducted under fasting conditions. A total of 32 eligible subjects were randomly administered a single dose of a 200-mg generic or branded pazopanib tablet with a 16-day washout period. Blood samples were collected before and up to 72 hours after dosing. Pharmacokinetic parameters were analyzed with noncompartmental analysis. Safety assessments included physical examinations, laboratory tests, and adverse events reporting. Maximum plasma concentration (C ), area under the plasma concentration-time curve (AUC) from zero to the last quantifiable concentration (AUC ), and AUC from zero to infinity (AUC ) were similar between the generic and branded products (all P > .05). The 90% confidence intervals of the geometric mean ratio of the test/reference products for C , AUC , and AUC were 89.1%-117.1%, 81.9%-108.5%, and 82.4%-109.6%, respectively. There were no serious adverse events during the study. The newly developed generic pazopanib tablet was bioequivalent to the reference product under fasting conditions. Both formulations were well tolerated in healthy Chinese volunteers.
Topics: Area Under Curve; Biological Availability; China; Cross-Over Studies; Drugs, Generic; Humans; Indazoles; Pyrimidines; Sulfonamides; Tablets; Therapeutic Equivalency
PubMed: 35384398
DOI: 10.1002/cpdd.1096 -
Seminars in Oncology Feb 1997The combination of carboplatin and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has been found to be highly active, to offer convenience of... (Review)
Review
The combination of carboplatin and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has been found to be highly active, to offer convenience of administration and better potential for dose escalation, and to produce less nonhematologic toxicity than standard therapy with cisplatin plus paclitaxel. Increased myelosuppression was anticipated to be a disadvantage of the carboplatin/paclitaxel combination, although it was expected to affect mainly platelets. Studies to date of the paclitaxel/carboplatin combination suggest the combination has a relatively benign effect on platelets compared with single-agent carboplatin. Previous pharmacokinetic studies have suggested that the measured area under the plasma carboplatin concentration-time curve is significantly less than that predicted by dosing formulas based on glomerular filtration rates. Newer evidence, however, contradicts these findings. This review examines the evidence of both a pharmacodynamic and a pharmacokinetic interaction between carboplatin and paclitaxel that has a sparing effect on platelets. It further assesses methodologic differences in methods used to estimate glomerular filtration. Paclitaxel appears to offer some protective effect for carboplatin-induced thrombocytopenia, although the two drugs do not interact pharmacokinetically. The apparent deviations of the achieved carboplatin area under the plasma concentration-time curve from that predicted by a dosing formula are thought to be due to differences in the methodology used to estimate renal function and measure creatinine. Any interaction between the two drugs most likely occurs at the level of the megakaryocyte.
Topics: Antineoplastic Combined Chemotherapy Protocols; Area Under Curve; Carboplatin; Drug Interactions; Glomerular Filtration Rate; Humans; Paclitaxel; Thrombocytopenia
PubMed: 9045345
DOI: No ID Found -
Voprosy Meditsinskoi Khimii 2002Pharmacokinetic properties of benzimidazole derivatives drug possessing antipsychotic, actoprotector, antiarrhythmic, antiulcerogenic, antiallergic, uricosuric,... (Review)
Review
Pharmacokinetic properties of benzimidazole derivatives drug possessing antipsychotic, actoprotector, antiarrhythmic, antiulcerogenic, antiallergic, uricosuric, anthelmintic activities have been summarized. Pharmacokinetics of benzimidazole derivatives used in veterinary practice as anthelmintic drugs is also considered. Benzimidazoles derivatives are characterised by multicompartment and ambiguous pharmacokinetic models. The derivatives of benzimidazoles are subjected to the first pass metabolism in the liver, and, therefore, they are converted to both active, and inactive metabolites. It is necessary to take into account for coadministration of benzimidazoles with other drugs. Hepatoduodenal circulation and repeated adsorption of unchanged drug and its metabolites in the gut is observed for benzimidazole. Many derivatives of benzimidazoles are characterised by rather low absolute bioavailability during peroral intake (from 2 up to 60%). Benzimidazsole derivative may bind to proteins and cell elements of blood. More often pharmacokinetic profile of benzimidazoles is linear for low doses, however, at high doses the linearity is lost. For animals and men pharmacokinetic models are always nearly identical.
Topics: Animals; Benzimidazoles; Biological Availability; Humans; Intestinal Absorption; Veterinary Drugs
PubMed: 12243082
DOI: No ID Found -
Biomedical Chromatography : BMC Jun 2023Fluvoxamine is a selective serotonin reuptake inhibitor commonly used for various types of depression. The purpose of this study was to evaluate the pharmacokinetics and... (Randomized Controlled Trial)
Randomized Controlled Trial
Fluvoxamine is a selective serotonin reuptake inhibitor commonly used for various types of depression. The purpose of this study was to evaluate the pharmacokinetics and bioequivalence of fluvoxamine maleate tablets orally on an empty stomach and after a meal in healthy adult Chinese subjects and to preliminarily evaluate their safety. A single-center, randomized, open-label, two-drug, two-period, crossover, single-dose trial protocol was designed. Sixty healthy Chinese participants were enrolled and randomly classified into fasting (n = 30) and fed groups (n = 30). Each week, subjects took fluvoxamine maleate tablets 50 mg orally once as a test preparation or as a reference preparation on an empty stomach/after meals. To evaluate the bioequivalence of test and reference tables, the concentration of fluvoxamine maleate in the plasma of the subjects at different time points after administration was detected by liquid chromatography-tandem mass spectrometry, and pharmacokinetic parameters including the maximum plasma drug concentration (C ), the time to reach maximum concentration (T ), the area under the plasma concentration-time curve from time 0 to the last measurable concentration (AUC ) and the area under the plasma concentration-time curve from time 0 to infinity (AUC ) were calculated. Our data revealed that the 90% confidence intervals of the geometric mean ratio of the test or reference drugs for the C , AUC and AUC fell within the acceptance range for bioequivalence (92.30-102.77%). The absorption, measured by AUC, did not show a significant difference between the two groups. There were no suspected serious adverse reactions or serious adverse events over the entire trial. Our results demonstrated that the test and reference tablets were bioequivalent under fasting and fed conditions.
Topics: Adult; Humans; Area Under Curve; China; Cross-Over Studies; East Asian People; Fasting; Fluvoxamine; Healthy Volunteers; Tablets; Tandem Mass Spectrometry; Therapeutic Equivalency
PubMed: 36849133
DOI: 10.1002/bmc.5613 -
Biological Trace Element Research Jan 2019Magnesium is an element of great importance functioning because of its association with many cellular physiological functions. The magnesium content of foods is...
Magnesium is an element of great importance functioning because of its association with many cellular physiological functions. The magnesium content of foods is gradually decreasing due to food processing, and magnesium supplementation for healthy living has become increasingly popular. However, data is very limited on the bioavailability of various magnesium preparations. The aim of this study is to investigate the bioavailability of five different magnesium compounds (magnesium sulfate, magnesium oxide, magnesium acetyl taurate, magnesium citrate, and magnesium malate) in different tissues. Following a single dose 400 mg/70 kg magnesium administration to Sprague Dawley rats, bioavailability was evaluated by examining time-dependent absorption, tissue penetration, and the effects on the behavior of the animals. Pharmacokinetically, the area under the curve calculation is highest in the magnesium malate. The magnesium acetyl taurate was found to have the second highest area under the curve calculation. Magnesium acetyl taurate was rapidly absorbed, able to pass through to the brain easily, had the highest tissue concentration level in the brain, and was found to be associated with decreased anxiety indicators. Magnesium malate levels remained high for an extended period of time in the serum. The commonly prescribed dietary supplements magnesium oxide and magnesium citrate had the lowest bioavailability when compared to our control group. More research is needed to investigate the bioavailability of magnesium malate and acetyl taurate compounds and their effects in specific tissues and on behavior.
Topics: Animals; Area Under Curve; Biological Availability; Dietary Supplements; Magnesium Compounds; Male; Rats; Rats, Sprague-Dawley; Time Factors
PubMed: 29679349
DOI: 10.1007/s12011-018-1351-9 -
Zhongguo Yi Xue Ke Xue Yuan Xue Bao.... Feb 2019Objective To explore the pharmacokinetics of nimodipine in plasma of rats after intraocular administration.Methods Totally 135 SD rats were randomly divided into three...
Objective To explore the pharmacokinetics of nimodipine in plasma of rats after intraocular administration.Methods Totally 135 SD rats were randomly divided into three groups according to drug administration routes:intraocular(io group),intravenous (iv group),and intragastric (ig group). The doses were 5.0 mg/kg for IO and IV groups and 10.0 mg/kg for IG group. The serum nimodipine level was analyzed by high performance liquid chromatography. The main pharmacokinetic parameters were calculated and compared.Results The pharmacokinetic parameters in io group were as follows:C:0.52 mg/ml;t:5.0 min;and AUC:21.10 mg/(ml·min). The main pharmacokinetic parameters in iv group were as follows:C:3.62 mg/ml;and AUC:52.58 mg/(ml·min). The main pharmacokinetic parameters in ig group were as follows:C:0.20 mg/ml;t:5.0 min;and AUC:5.98 mg/(ml·min).Conclusions Nimodipine is rapidly absorbed after io administration,and the ophthalmic formulation has a higher bioavailability than the oral solution. Therefore,the io route may help to improve the treatment effectiveness of cardiovascular diseases.
Topics: Administration, Intravenous; Administration, Oral; Animals; Area Under Curve; Biological Availability; Chromatography, High Pressure Liquid; Nimodipine; Rats; Rats, Sprague-Dawley
PubMed: 30837043
DOI: 10.3881/j.issn.1000-503X.10536 -
European Journal of Drug Metabolism and... 1993The paper deals with the most relevant aspects related to the pharmacokinetics of endogenous substances. Two different views are presented in order to focus on two... (Review)
Review
The paper deals with the most relevant aspects related to the pharmacokinetics of endogenous substances. Two different views are presented in order to focus on two aspects of the problem, the physiological background of these substances and the need for empirical or tailored models to process pharmacokinetic data. Very often endogenous substances follow saturable enzyme biotransformation, reversible interconversion, active and diffusional transports, renal threshold, endogenous synthesis plus dietary supply with possible balancement between these two factors, feedback processes, asymmetric distribution with specific body storage, and gender differences. These mechanisms allow the body to preserve and restore homeostatic equilibria of endogenous substances. The most relevant problem in pharmacokinetics of these substances is the presence of baseline concentration which needs to be carefully defined also for possible rhythms related to age, sex, diet, night and day periods. Theoretical considerations are presented for the management of pharmacokinetic analysis of these substances, which only rarely follow linear processes. Throughout the text various practical examples are considered.
Topics: Animals; Biological Availability; Female; Humans; Male; Models, Biological; Pharmacokinetics
PubMed: 8335042
DOI: 10.1007/BF03220010 -
Journal of Pharmaceutical Sciences Mar 2010The significance of plasma protein binding on drug efficacy and, subsequently, the clinical relevance of changes in protein binding has been controversially discussed... (Review)
Review
The significance of plasma protein binding on drug efficacy and, subsequently, the clinical relevance of changes in protein binding has been controversially discussed for decades. The uncertainty concerning the impact of plasma protein binding on a drug's pharmacological activity is, in part, related to the approach used when investigating and interpreting protein binding effects in vitro and in vivo. Frequently, a generalized one-size-fits-all approach, such as "protein binding does matter/does not matter," may not be applicable. An appropriate analysis requires careful consideration of both pharmacokinetic and pharmacodynamic processes, as they both contribute to the safety and efficacy of drugs. Therefore, the aim of this article is to provide a concise review of the theoretical concepts of protein binding, and to discuss relevant examples where applicable.
Topics: Animals; Biological Availability; Drug Administration Routes; Drug Evaluation, Preclinical; Half-Life; Humans; In Vitro Techniques; Metabolic Clearance Rate; Models, Statistical; Pharmacokinetics; Pharmacology; Protein Binding; Tissue Distribution
PubMed: 19852037
DOI: 10.1002/jps.21916 -
Revising Pharmacokinetics of Oral Drug Absorption: II Bioavailability-Bioequivalence Considerations.Pharmaceutical Research Aug 2021To explore the application of the parameters of the physiologically based finite time pharmacokinetic (PBFTPK) models subdivided in first-order (PBFTPK) and...
PURPOSE
To explore the application of the parameters of the physiologically based finite time pharmacokinetic (PBFTPK) models subdivided in first-order (PBFTPK) and zero-order (PBFTPK) models to bioavailability and bioequivalence. To develop a methodology for the estimation of absolute bioavailability, F, from oral data exclusively.
METHODS
Simulated concentration time data were generated from the Bateman equation and compared with data generated from the (PBFTPK)and (PBFTPK) models. The blood concentration C(τ) at the end of the absorption process τ, was compared to C; the utility of [Formula: see text] and [Formula: see text] in bioequivalence assessment was also explored. Equations for the calculation of F from oral data were derived for the (PBFTPK) and (PBFTPK) models. An estimate for F was also derived from an areas proportionality using oral data exclusively.
RESULTS
The simulated data of the (PBFTPK) models exhibit rich dynamics encountered in complex drug absorption phenomena. Both (PBFTPK) and (PBFTPK) models result either in C = C(τ) or C > C(τ) for rapidly- and not rapidly-absorbed drugs, respectively; in the latter case, C(τ) and τ are meaningful parameters for drug's rate of exposure. For both (PBFTPK) and (PBFTPK) models, [Formula: see text] or portions of it cannot be used as early exposure rate indicators. [Formula: see text] is a useful parameter for the assessment of extent of absorption for very rapidly absorbed drugs. An estimate for F for theophylline formulations was found close to unity.
CONCLUSION
The (PBFTPK) and (PBFTPK) models are more akin to in vivo conditions. Estimates for F can be derived from oral data exclusively.
Topics: Administration, Oral; Area Under Curve; Biological Availability; Humans; Intestinal Absorption; Models, Biological; Pharmacokinetics; Therapeutic Equivalency
PubMed: 34341958
DOI: 10.1007/s11095-021-03078-w