scholarly journals Effects of Vitamin D Plus Calcium Supplements on Pharmacokinetics of Isoflavones in Thai Postmenopausal Women

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Supanimit Teekachunhatean ◽  
Paveena Pongnad ◽  
Noppamas Rojanasthein ◽  
Maleeya Manorot ◽  
Chaichan Sangdee
Keyword(s):  
Vitamin D ◽  
Single Dose ◽  
Plasma Concentration ◽  
Postmenopausal Women ◽  
Plasma Concentrations ◽  
Pharmacokinetic Parameters ◽  
Calcium Supplements ◽  
Maximal Plasma Concentration ◽  
Maximal Plasma ◽  
To Receive

The objective of this study was to determine the effects of vitamin D3plus calcium supplements (D3-calcium) on pharmacokinetics of isoflavones in Thai postmenopausal women. This study was an open-labeled, randomized three-phase crossover study. Twelve healthy subjects were randomized to receive one of the following regimens: (a) a single dose of isoflavones, (b) a single dose of isoflavones, and D3-calcium, or (c) continuous D3-calcium for 7 days followed by a single dose of isoflavones on the 8th day. After a washout period, subjects were switched to receive the 2 remaining regimens according to their randomized sequences. Blood samples were collected before dose and at specific time points until 32 hours after isoflavone administration. Plasma was treated with β-glucuronidase/sulfatase to hydrolyze glucuronide and sulfate conjugates of daidzein and genistein. Plasma concentrations of daidzein and genistein were determined by high performance liquid chromatography. The estimated pharmacokinetic parameters of isoflavones were time to maximal plasma concentration (Tmax), maximal plasma concentration (Cmax), half-life (t1/2) and area under the plasma concentration-time curve (AUC).Tmaxof daidzein and genistein after regimen B was significantly longer than that of regimen A. Other pharmacokinetic parameters of daidzein and genistein obtained following the three regimens were not significantly different.

Pharmacokinetics of low-dose and high-dose buprenorphine in cats after rectal administration of different formulations

2018 ◽  
Vol 21 (10) ◽  
pp. 938-943
Author(s):  
Maike Schroers ◽  
Andrea Meyer-Lindenberg ◽  
Sven Reese ◽  
Britta Dobenecker ◽  
Korbinian Pieper
Keyword(s):  
Plasma Concentration ◽  
Low Dose ◽  
Ph Value ◽  
Plasma Concentrations ◽  
Rectal Administration ◽  
High Dose ◽  
Time Curve ◽  
Maximal Plasma Concentration ◽  
Wide Range ◽  
Maximal Plasma

Objectives A prospective experimental study was performed in nine young healthy cats to investigate a pharmacokinetic profile and the clinical relevance of rectally administered buprenorphine. Rectal pH value was measured in all nine cats. Methods Blood was collected 15, 30, 60, 90, 120, 240 and 480 mins and 24 h after the rectal administration of a suppository and a gel at doses between 0.02 mg/kg and 0.1 mg/kg buprenorphine to determine the plasma concentration of buprenorphine. Rectal pH was measured with pH paper. Results Upon pharmacokinetic non-compartment analysis of high-dose buprenorphine (0.1 mg/kg), average maximal plasma concentration was found to be 1.13 ng/ml, time to maximal plasma concentration was 45 mins and area under the plasma concentration–time curve was 94.19 ng*min/ml, representing low but potential bioavailability. Mean residual time was 152.2 mins and the half-life was 92.6 mins. A wide range of plasma concentrations within the cohort was measured and two of the cats had to be excluded from statistical analysis owing to incomplete uptake. Vital parameters of all cats were considered to be normal but three of the cats showed mydriasis up to 8 h after application. After the administration of a low-dose suppository or a rectal gel (0.02 mg/kg) within pilot studies, no buprenorphine was detected in cat plasma. Rectal pH in all cats was between 7.7 and 8. Conclusions and relevance The rectal application of buprenorphine at a dose of 0.1 mg/kg revealed a potential but weak uptake in cats. Regarding effective concentrations in previous pharmacokinetic investigations, rectal administration is currently not recommended for good provision of opioid analgesia in cats. Pharmacological investigations of formulation and galenics in order to improve the rectal bioavailability of buprenorphine remain to be clarified before further dose-finding and pharmacokinetic/pharmacodynamic studies are performed.

scholarly journals Effect of Oral Coadministration of Ascorbic Acid with Ling Zhi Preparation on Pharmacokinetics of Ganoderic Acid A in Healthy Male Subjects: A Randomized Crossover Study

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Patcharanee Tawasri ◽  
Chadarat Ampasavate ◽  
Somsak Tharatha ◽  
Natthakarn Chiranthanut ◽  
Supanimit Teekachunhatean
Keyword(s):  
Ascorbic Acid ◽  
Single Dose ◽  
Plasma Concentration ◽  
Crossover Study ◽  
Biologically Active ◽  
Pharmacokinetic Parameters ◽  
Healthy Male ◽  
Ganoderic Acid ◽  
To Receive ◽  
Male Subjects

The objective of this randomized, open-label, single-dose, two-phase crossover study was to determine the effect of ascorbic acid on pharmacokinetics of ganoderic acid A, an important biologically active triterpenoid compound with anticancer activities, following oral administration of water extract of fruiting bodies of Ling Zhi in 12 healthy male subjects. Each subject was randomized to receive either one of the two regimens: (1) a single dose of 3,000 mg of the Ling Zhi preparation or (2) a single dose of 3,000 mg of the Ling Zhi preparation in combination with 2,500 mg of ascorbic acid. After a washout period of at least two weeks, subjects were switched to receive the alternate regimen. Blood samples were collected in each phase immediately before dosing and at specific time points for 8 hours after dosing. Plasma ganoderic acid A concentrations were quantified using liquid chromatography-mass spectrometry (LC-MS). The pharmacokinetic parameters analyzed were maximal plasma concentration (Cmax), time to reach peak concentration (Tmax), area under the plasma concentration-time curve (AUC), and half-life (t1/2). An oral coadministration of ascorbic acid with Ling Zhi preparation did not significantly alter the pharmacokinetic parameters of ganoderic acid A in healthy male subjects.

Continuation Therapy with Amitriptyline in Depression

1978 ◽  
Vol 133 (1) ◽  
pp. 28-33 ◽  
Author(s):  
A. Coppen ◽  
K. Ghose ◽  
S. Montgomery ◽  
V. A. Rama Rao ◽  
J. Bailey ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Plasma Concentrations ◽  
Antidepressant Medication ◽  
Depressive Illness ◽  
Continuation Therapy ◽  
One Year ◽  
To Receive

SummaryThirty-two patients who had responded to amitriptyline (150 mg daily) when suffering from a depressive illness were allocated either to receive placebo or to remain on the same medication for one year.Plasma concentrations of the drug were regularly estimated. There was no correlation between plasma concentration and subsequent residual affective morbidity. In spite of considerable encouragement, three of the patients did not take the prescribed amitriptyline and they all relapsed. Five out of sixteen patients who received placebo relapsed. None of the patients who continued to take amitriptyline relapsed.It is emphasized that the patients studied were selected, inasmuch as they were apparent responders to amitriptyline. It is concluded that this group of patients should continue to be treated with antidepressant medication for eight months after apparent recovery, and care should be taken to ensure the patients' compliance.

scholarly journals Variable Absorption of Clavulanic Acid After an Oral Dose of 25 mg/kg of Clavubactin® and Synulox® in Healthy Cats

2002 ◽  
Vol 2 ◽  
pp. 1369-1378 ◽  
Author(s):  
Tom B. Vree ◽  
Eric Dammers ◽  
Eri van Duuren
Keyword(s):  
Single Dose ◽  
Plasma Concentration ◽  
Oral Dose ◽  
Clavulanic Acid ◽  
Phase I Study ◽  
Pharmacokinetic Parameters ◽  
High Efficacy ◽  
Dose Ratio ◽  
Concentration Time ◽  
Crossover Phase

The aims of this investigation were to calculate the pharmacokinetic parameters and to identify parameters, based on individual plasma concentration-time curves of amoxicillin and clavulanic acid in cats, that may govern the observed differences in absorption of both drugs. The evaluation was based on the data from plasma concentration-time curves obtained following a single-dose, open, randomised, two-way crossover phase-I study, each involving 24 female cats treated with two Amoxi-Clav formulations (formulation A was Clavubactin® and formulation was B Synulox® ; 80/20 mg, 24 animals, 48 drug administrations). Plasma amoxicillin and clavulanic acid concentrations were determined using validated bioassay methods. The half-life of elimination of amoxicillin is 1.2 h (t1/2= 1.24 ± 0.28 h, Cmax= 12.8 ± 2.12 μg/ml), and that of clavulanic acid 0.6 h (t1/2= 0.63 ± 0.16 h, Cmax= 4.60 ± 1.68 μg/ml). There is a ninefold variation in the AUCtof clavulanic acid for both formulations, while the AUCtof amoxicillin varies by a factor of two. The highest clavulanic acid AUCtvalues indicate the best absorption; all other data indicate less absorption. Taking into account that the amoxicillin–to–clavulanic acid dose ratio in the two products tested was 4:1, the blood concentration ratios may actually vary much more, apparently without compromising the products’ high efficacy against susceptible microorganisms.

Comparative Pharmacokinetic of Three Sulfadiazine Suspensions by Oral Administration in Chickens

2016 ◽  
Vol 8 (2) ◽  
pp. 122
Author(s):  
Zhi-Qiang Wang ◽  
Han-Song Li ◽  
Xia Xiao ◽  
Jian-Bing Wang
Keyword(s):  
Plasma Concentration ◽  
Broiler Chickens ◽  
High Performance ◽  
Area Under The Curve ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Peak Time ◽  
Comparative Pharmacokinetic ◽  
Elimination Half ◽  
Maximal Plasma

<p>The chemotherapeutics, sulfadiazine (SDA) and trimethoprim (TMP), are extensively used in a variety of animal species. In this study, a pharmacokinetic analysis was performed to compare the bioequivalence of a combined SDA and TMP product against existing licensed SDA and TMP formulations in broiler chickens. Three groups of 15 birds were administered a single dose of either the test formulation or a reference oral suspension. The plasma concentration of SDA and TMP were determined by reverse-phase high performance liquid chromatography (HPLC), and the maximal plasma concentration (C<sub>max</sub>), area under the curve (AUC), the peak time (T<sub>max</sub>), mean residence time (MRT) and elimination half-life (T<sub>1/2</sub>), were calculated for SDA. The combined formulation I and II reference suspension exhibited almost identical concentration-time curves, and ANOVA analyses of the pharmacokinetic parameters identified no significant differences between the reference preparations and the test one. Furthermore the AUC and C<sub>max</sub> values of the SDA active ingredient were not significantly different. The I formulation was bioequivalent with both II and III (80-125% and 70–143%, respectively, at the 90% confidence interval). In conclusion, the combined SDA and TMP product was bioequivalent with both existing commercially available SDA suspensions and can be used interchangeably in veterinary medical practice.</p>

Managing plasma P concentrations in beef heifers with a slow release vitamin D supplementation

2020 ◽  
Vol 60 (5) ◽  
pp. 610
Author(s):  
N. W. Tomkins ◽  
R. Elliott ◽  
J. J. McGrath ◽  
T. Schatz
Keyword(s):  
Vitamin D ◽  
Plasma Concentration ◽  
Growth Rates ◽  
Slow Release ◽  
Plasma Concentrations ◽  
Vitamin D Supplementation ◽  
Placebo Control ◽  
Elevated Plasma ◽  
Hydroxyvitamin D ◽  
Rumen Bolus

Context In extensive northern grazing systems, supplementation of P is recommended to maximise cattle growth rates and reproduction. Improving the absorption of P for the animal by influencing metabolic pathways has the potential to improve both the productivity and profitability of extensive livestock enterprises. Aims This study evaluated the efficacy of rumen bolus containing 25-hydroxyvitamin D (25OHD), commercially available as Hy-D®, and/or monensin on blood P and Ca concentrations in young cattle. Methods A total of 84 heifers, initial liveweight (mean ± s.e.m.) 184 ± 2.0 kg, were allocated to four groups, dosed with one of four slow release bolus: (1) placebo (control), (2) monensin (120 mg/day), (3) Hy-D® (6 mg/day), or (4) monensin with Hy-D®, and managed on a common unimproved native pasture from August 2012 to February 2013. On four occasions postdosing, liveweight, hip height and body condition scores were recorded, and individual faecal and jugular blood samples were collected. Key results Supplementation with monensin had a significant effect (P &lt; 0.05) on average daily gains for the first 25 days. Interactions between 25OHD and monensin and time × monensin were also significant (P &lt; 0.05). After 188 days, heifers receiving monensin or 25OHD + monensin were 5 and 10 kg heavier respectively, compared with their counterparts in the control and 25OHD groups. Plasma P concentrations at 25 days were 6.6 mg/dL, then increased to between 8.5 and 9.0 mg/dL and maintained this level for up to 109 days with a bolus releasing 6.0 mg/day 25OHD. Conclusions The study demonstrated that sustained and elevated plasma concentrations of both 25OHD and P, compared with control animals, can be achieved. The slow release rumen bolus maintained an elevated plasma concentration of 25OHD, and indicated that a target plasma concentration for 25OHD for increasing P absorption in beef cattle is between 200 and 300 ng/mL. Implications Supplementation of a metabolite of vitamin D influences P metabolism in Brahman heifers under grazing conditions. Integration with standard supplementation practices would optimise growth rates and reproductive performance.

Clinical Rules for Phenytoin Dosing

1993 ◽  
Vol 27 (10) ◽  
pp. 1169-1173 ◽  
Author(s):  
Michael D. Privitera
Keyword(s):  
Plasma Concentration ◽  
Plasma Concentrations ◽  
Test Group ◽  
Patient Data ◽  
Pharmacokinetic Parameters ◽  
Concentration Data ◽  
Simple Method ◽  
Actual Patient ◽  
Initial Plasma ◽  
Clinical Rules

OBJECTIVE: To develop simple clinical rules for dosing phenytoin (PHT) using computer simulations, then to test the rules for accuracy and safety on actual patient data. DESIGN: Patients with steady-state PHT plasma concentrations at least two different PHT doses were identified from three separate sources of patient data. A computerized dosing program calculated pharmacokinetic parameters using Bayesian methodology, then predicted how many patients were likely to reach potentially toxic PHT plasma concentrations when their daily dosage was increased by 30, 50, or 100 mg. Dosing rules were developed to allow fewer than ten percent of resultant plasma concentrations to exceed 25 μg/mL. The dosing rules then were tested on dose/plasma concentration data from a separate group of patients. SETTING: All patients were being treated by neurologists either as outpatients or inpatients. PATIENTS: All patients were adults with epilepsy being treated with PHT; none had clinically significant renal or hepatic disease. Patients for the computer simulation were from three sources: (1) patients who had an initial PHT plasma concentration <10 μg/mL and required a dosage increase; (2) patients admitted to the hospital for PHT intoxication; and (3) patients who required consultations specifically for PHT dosing. Patients on whom the dosing rules were tested were part of a prospective, randomized trial of antiepileptic drug safety and efficacy. MAIN OUTCOME MEASURES: Successful dosing rules allowing fewer than ten percent of resulting plasma concentrations in the test group to exceed 25 μg/mL. RESULTS: The simulations used 167 actual dose/plasma concentration pairs from 45 patients. The resulting dosing rules were: increase the dosage by 100 mg/d if the initial plasma concentration was <7 μg/mL; increase the dosage by 50 mg/d if the initial plasma concentration is 7 to <12 μg/mL; increase the dosage by 30 mg/d if the initial plasma concentration is ≥12 μg/mL. The rules were tested on 129 50- or 100-mg dosage increases in 77 patients. All 53 dosage increases that were within the dosing rules produced plasma concentrations <25 μg/mL, whereas 36 percent (27 of 74) of the dosage increases that exceeded the dosing rules produced plasma concentrations >25 μg/mL. CONCLUSIONS: The proposed dosing rules are a simple method for clinicians to estimate PHT dosage changes and appear to be safe and accurate when applied retrospectively to actual patient data.

scholarly journals Absorption of red clover isoflavones in human subjects: results from a pilot study

2010 ◽  
Vol 103 (11) ◽  
pp. 1569-1572 ◽  
Author(s):  
Ronald Maul ◽  
Sabine E. Kulling
Keyword(s):  
Single Dose ◽  
Plasma Concentration ◽  
Pilot Study ◽  
Enzymatic Hydrolysis ◽  
Human Subjects ◽  
Plasma Concentrations ◽  
Red Clover ◽  
First Time ◽  
High Bioavailability ◽  
Present Pilot Study

In addition to soya-derived preparations, red clover-based dietary supplements have gained considerable interest as an alternative isoflavone (IF) source. While metabolism and bioavailability of the main IF from both sources have already been investigated, studies are still lacking on the biokinetic behaviour of IF, which are present in red clover in minor amounts. In the present pilot study, in which seven volunteers ingested a single dose of a commercial red clover dietary supplement, we focused on the absorption of three such IF, irilone (IRI), prunetin (PRUN) and pseudobaptigenin (PBAP). The compounds were measured as aglycones after enzymatic hydrolysis. A single intake of an amount of as low as 3·8 mg IRI (out of 38·8 mg IF in total) resulted in an IRI plasma concentration of 0·35 (sd 0·16) μm at 6.5 h post-ingestion. Compared to the plasma concentrations found for daidzein (0·39 μm) and genistein (0·06 μm), expected to be the main IF metabolites in plasma, the present findings indicate that IRI might possess a relatively high bioavailability. Furthermore, PRUN and PBAP were detected in human plasma for the first time.

scholarly journals Bioequivalence of levamlodipine besylate tablets in healthy Chinese subjects: A single-dose and two-period crossover randomized study

2020 ◽  
Author(s):  
Li Xin ◽  
Chenjing Wang ◽  
Ting Li ◽  
Yanping Liu ◽  
Shuqin Liu ◽  
...  
Keyword(s):  
Single Dose ◽  
Randomized Study ◽  
Plasma Concentrations ◽  
Bioequivalence Study ◽  
Pharmacokinetic Parameters ◽  
Open Label ◽  
Liquid Chromatography Tandem Mass ◽  
The Mean ◽  
Healthy Chinese ◽  
Chinese Subjects

Abstract Background: Levamlodipine, a calcium channel blocker, has been show act as a cardiovascular drug. To compare the pharmacokinetic parameters between levamlodipine (test formulation) at a single dose of 5 mg and amlodipine (reference formulation) at a single dose of 10 mg, the bioequivalence study was carried out.Methods: A single-dose randomized, open-label, two-period crossover study was designed in healthy Chinese subjects. 48 subjects were divided into fasted and fed groups equally. The subjects randomly received the test or reference formulations at the rate of 1:1. Following a 21-day washout period, the alternative formulations were received. The blood samples were collected at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 24, 36, 48, 72, 96, 120, 144, 168 hours later. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was applied to determine the plasma concentrations of levamlodipine. Adverse events were recorded.Results: The 90% confidence intervals (CIs) of the ratio of geometric means (GMRs) of Cmax, AUC0-t, and AUC0-∞ under both fasted and fed conditions were within the prespecified bioequivalence limits between 80~125%. Under fasted conditions, 24 subjects were enrolled and completed the study. The mean Cmax was (2.70±0.49) ng/mL, AUC0-t was (141.32±36.24) ng×h/mL and AUC0-∞ was (157.14±45.65) ng×h/mL after a single dose of 5 mg levamlodipine. The mean Cmax was (2.83±0.52) ng/mL, AUC0-t was (153.62±33.96) ng×h/mL and AUC0-∞ was (173.05±41.78) ng×h/mL after a single dose of 10 mg amlodipine. Under fed conditions, 24 subjects were enrolled and completed the study. The mean Cmax was (2.73±0.55) ng/mL, AUC0-t was (166.93±49.96) ng×h/mL and AUC0-∞ was (190.99±70.89) ng×h/mL after a single dose of 5 mg levamlodipine. The mean Cmax was (2.87±0.81) ng/mL AUC0-t was (165.46±43.58) ng×h/mL and AUC0-∞ was (189.51±64.70) ng×h/mL after a single dose of 10 mg amlodipine. Serious adverse event was not observed.Conclusion: The trial confirmed that levamlodipine at a single dose of 5 mg and amlodipine at a single dose of 10 mg were bioequivalent under both fasted condition and fed condition.Trial registration: Cinicaltrials, NCT04411875. Registered 3 June 2020 - Retrospectively registered, https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0009W1Q&selectaction=Edit&uid=U00050YQ&ts=3&cx=-6iqkm8

scholarly journals Gender differences in concentration of itraconazole and hydroxyitraconazole

2021 ◽  
Vol 27 (1) ◽  
pp. 7-18
Author(s):  
Tijana Stanojković ◽  
Milijana Miljković ◽  
Nemanja Rančić ◽  
Aleksandra Kovačević ◽  
Viktorija Dragojević-Simić
Keyword(s):  
Single Dose ◽  
Plasma Concentrations ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Time Intervals ◽  
Chromatography Method ◽  
Oral Application ◽  
First Pass ◽  
Liquid Chromatography Method ◽  
Pass Through

Introduction: Itraconazole is an antifungal drug belonging to the triazole group. After oral application, it is rapidly absorbed, but its bioavailability is reduced due to an intensive first-pass through the liver metabolism effect. A large number of metabolites (the most important of which is hydroxyitraconazole) are produced by isoform CYP3A4 of cytochrome P450. The variability of itraconazole pharmacokinetics is the result of numerous factors that have not yet been fully clarified. Our study aimed to investigate the influence of gender on itraconazole and hydroxyitraconazole plasma concentrations in healthy adults after an oral application of a single dose of itraconazole. Methods: Pharmacokinetic analysis was performed after oral administration of itraconazole in a single dose of 100 mg to 22 male and 16 female healthy volunteers. Blood samples were collected before taking the drug and at appropriate time intervals up to 72 hours later. Itraconazole and hydroxyitraconazole concentrations were determined using a validated liquid chromatography method with mass spectrometric detection (LC-MS/MS) and their pharmacokinetic parameters were calculated by using the Kinetica programme, version 5.0: Cmax, Tmax, PIK (0-72), PIK (0-∞), T1/2, and Ke. Results: The median values of both itraconazole and hydroxyitraconazole were lower in women in comparison to men during the whole period of observation. Moreover, median values of Cmax, PIK(0-72) and PIK(0-∞) parameters were also significantly lower in women, concerning both itraconazole (p=0.005, 0.036 and 0.036, respectively) and its metabolite (p=0.004, 0.010 and 0.044, respectively). Elimination parameters - T1/2 and Ke did not differ between genders. Conclusion: Women were less exposed to itraconazole and its active metabolite than men following an oral application of the drug, possibly as a result of lower bioavailability due to a more intense pre-systemic metabolism, as a result of a higher expression and/or activity of the isoform enzyme, which metabolises itraconazole, and which would need to be confirmed by pharmacogenomic analysis.

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