Co-administration of Dalbergia odorifera Increased Bioavailability of Salvia miltiorrhizae in Rabbits

2007 ◽  
Vol 35 (05) ◽  
pp. 831-840 ◽  
Author(s):  
Xiaohui Zheng ◽  
Xinfeng Zhao ◽  
Shixiang Wang ◽  
Kai Luo ◽  
Yinmao Wei ◽  
...  
Keyword(s):  
High Performance ◽  
Salvia Miltiorrhiza ◽  
Blood Stasis ◽  
Time Curve ◽  
Healthy Group ◽  
First Order ◽  
Concentration Time ◽  
Salvia Miltiorrhizae ◽  
Dalbergia Odorifera ◽  
Compartment Open Model

This study was to investigate the effect of Dalbergia odorifera (DO) on the pharmacokinetics of Danshensu in Salvia miltiorrhiza (SM) in healthy rabbits and rabbits with qi-stagnancy and blood stasis. Thirty two healthy rabbits were involved in the whole experiment. Qi-stagnancy and blood stasis rabbits were obtained by treating the limbs of 16 adnephrin rabbits in an ice-bath for 6.0 min. The rest of rabbits were equally divided into 2 healthy groups. One healthy group and 8 qi-stagnancy and blood stasis rabbits were orally administrated with SM (5.0 g/kg), and the other 8 healthy rabbits and 8 qi-stagnancy and blood stasis rabbits with SM (5.0 g/kg) coupled with DO (2.5 g/kg). The plasma (Danshensu) concentration–time curve was measured by high performance liquid chromatography (HPLC)-electrospray ionization (ESI)-trap mass (MS-MS). Danshensu in plasma was confirmed to be two-compartment open model with a first order absorption phase in all groups. Moreover, the area under curve (0-∞) of Danshensu was significantly increased both in healthy group and in qi-stagnancy and blood stasis group after administration of SM coupled with DO. This result was in accordance with the “Jun-Shi pairing herbs theory” of traditional Chinese medicine (TCM).

scholarly journals 1326. Vancomycin Area Under the Concentration-Time Curve (AUC) Estimation Using a Bayesian Approach Versus First-Order Pharmacokinetic Equations: A Pilot Study

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S673-S673
Author(s):  
Jeffrey Pearson ◽  
Yazed S Alsowaida ◽  
B S Pharm ◽  
David W Kubiak ◽  
Mary P Kovacevic ◽  
...  
Keyword(s):  
Pilot Study ◽  
Median Time ◽  
Bayesian Modeling ◽  
Surgical Prophylaxis ◽  
Time Curve ◽  
Team Members ◽  
First Order ◽  
Concentration Time ◽  
Study Team ◽  
Auc Estimation

Abstract Background Current guidelines endorse area under the concentration-time curve (AUC)-based monitoring over trough-only monitoring for systemic vancomycin. Vancomycin AUC can be estimated using either Bayesian modeling software or first-order pharmacokinetic (PK) calculations. The objective of this pilot study was to evaluate and compare the efficiency and feasibility of these two approaches for calculating the estimated vancomycin AUC. Methods A single-center crossover study was conducted in four medical/surgical units at Brigham and Women’s Hospital over a 3-month time period. All adult patients who received vancomycin were included. Patients were excluded if they were receiving vancomycin for surgical prophylaxis, were on hemodialysis, if vancomycin was being dosed by level, or if vancomycin levels were never drawn. The primary endpoint was the amount of time study team members spent calculating the estimated AUC and determining regimen adjustments with Bayesian modeling compared to first-order PK calculations. Secondary endpoints included the number of vancomycin levels drawn and the percent of those drawn that were usable for AUC calculations. Results One hundred twenty-four patients received vancomycin during the study, of whom 47 met inclusion criteria. The most likely reasons for exclusion were receiving vancomycin for surgical prophylaxis (n=40) or never having vancomycin levels drawn (n=32). The median time taken to assess levels in the Bayesian arm was 9.3 minutes [interquartile range (IQR) 7.8-12.4] versus 6.8 minutes (IQR 4.8-8.0) in the 2-level PK arm (p=0.004). However, if Bayesian software is integrated into the electronic health record (EHR), the median time to assess levels was 3.8 minutes (IQR 2.3-6.8, p=0.019). In the Bayesian arm, 30 of 34 vancomycin levels (88.2%) were usable for AUC calculations, compared to 28 of 58 (48.3%) in the 2-level PK arm. Conclusion With EHR integration, the use of Bayesian software to calculate the AUC was more efficient than first-order PK calculations. Additionally, vancomycin levels were more likely to be usable in the Bayesian arm, thereby avoiding delays in estimating the vancomycin AUC. Disclosures All Authors: No reported disclosures

scholarly journals Pharmacokinetics of Ethambutol under Fasting Conditions, with Food, and with Antacids

1999 ◽  
Vol 43 (3) ◽  
pp. 568-572 ◽  
Author(s):  
Charles A. Peloquin ◽  
Amy E. Bulpitt ◽  
George S. Jaresko ◽  
Roger W. Jelliffe ◽  
James M. Childs ◽  
...  
Keyword(s):  
Maximum Concentration ◽  
Pharmacokinetic Model ◽  
Mass Spectrometry Data ◽  
Gas Chromatography Mass Spectrometry ◽  
High Fat ◽  
Time Curve ◽  
First Order ◽  
Concentration Time ◽  
Males And Females ◽  
Fat Meal

ABSTRACT Ethambutol (EMB) is the most frequent “fourth drug” used for the empiric treatment of Mycobacterium tuberculosis and a frequently used drug for infections caused by Mycobacterium avium complex. The pharmacokinetics of EMB in serum were studied with 14 healthy males and females in a randomized, four-period crossover study. Subjects ingested single doses of EMB of 25 mg/kg of body weight under fasting conditions twice, with a high-fat meal, and with aluminum-magnesium antacid. Serum was collected for 48 h and assayed by gas chromatography-mass spectrometry. Data were analyzed by noncompartmental methods and by a two-compartment pharmacokinetic model with zero-order absorption and first-order elimination. Both fasting conditions produced similar results: a mean (± standard deviation) EMB maximum concentration of drug in serum (C max) of 4.5 ± 1.0 μg/ml, time to maximum concentration of drug in serum (T max) of 2.5 ± 0.9 h, and area under the concentration-time curve from 0 h to infinity (AUC0–∞) of 28.9 ± 4.7 μg · h/ml. In the presence of antacids, subjects had a mean C maxof 3.3 ± 0.5 μg/ml, T max of 2.9 ± 1.2 h, and AUC0–∞ of 27.5 ± 5.9 μg · h/ml. In the presence of the Food and Drug Administration high-fat meal, subjects had a mean C max of 3.8 ± 0.8 μg/ml, T max of 3.2 ± 1.3 h, and AUC0–∞ of 29.6 ± 4.7 μg · h/ml. These reductions in C max, delays inT max, and modest reductions in AUC0–∞ can be avoided by giving EMB on an empty stomach whenever possible.

scholarly journals Administration of aminoglycosides to hemodialysis patients immediately before dialysis: a new dosing modality.

1997 ◽  
Vol 41 (12) ◽  
pp. 2597-2601 ◽  
Author(s):  
H Matsuo ◽  
J Hayashi ◽  
K Ono ◽  
K Andoh ◽  
Y Andoh ◽  
...  
Keyword(s):  
High Performance ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Cellulose Triacetate ◽  
The Body ◽  
High Rate ◽  
Complete Disappearance ◽  
Time Curve ◽  
Once Daily ◽  
Ethylene Vinyl Alcohol ◽  
Concentration Time

We describe a new modality for administering aminoglycosides to hemodialysis (HD) patients, namely, a modification of the once-daily regimen which consists of administering the aminoglycosides over 60 min by drip infusion just before each HD session, with a preplanned peak concentration being reached at the beginning of the session and then with a rapidly decreasing concentration being achieved by the start of HD. The area under the concentration-time curve (AUC), i.e., the accumulation of the drug in the body, is thus minimized by this modality. Arbekacin (ABK) was given at a dose of 2 mg/kg of body weight to 10 HD patients infected with methicillin-resistant Staphylococcus aureus (MRSA) for 2 weeks (six sessions in total), resulting in the complete disappearance of MRSA in 5 patients. A high rate of elimination of ABK was attained for each patient while the patient was on HD (range, 0.20 to 0.42 h-1; mean 0.28 +/- 0.08 h-1) by using high-performance dialyzers provided with membranes made of either polymethylmethacrylate, cellulose triacetate (CTA), or ethylene vinyl alcohol. The best results were obtained with the CTA membrane, as revealed by the overall mass transfer coefficient (Ko). The AUC in the simulation model for the variation in the serum ABK concentration in this modality was calculated to be 40% of that of the conventional post-HD dosing modality, suggesting that a much higher dose could be administered to HD patients who receive HD thrice weekly (4 h per session), giving, e.g., 4 mg/kg initially and before the HD sessions, when there is an interval of 68 h from HD session to HD session, and giving 2 mg/kg before the other sessions.

scholarly journals Lack of Effect of Zafirlukast on the Pharmacokinetics of Azithromycin, Clarithromycin, and 14-Hydroxyclarithromycin in Healthy Volunteers

1999 ◽  
Vol 43 (5) ◽  
pp. 1152-1155 ◽  
Author(s):  
Kevin W. Garey ◽  
Charles A. Peloquin ◽  
Paul G. Godo ◽  
Anne N. Nafziger ◽  
Guy W. Amsden
Keyword(s):  
Steady State ◽  
Healthy Subjects ◽  
High Performance ◽  
Pharmacokinetic Parameters ◽  
Steady State Concentration ◽  
Open Label ◽  
Time Curve ◽  
Data Analyses ◽  
Concentration Time ◽  
State Concentration

ABSTRACT This randomized, open-label, crossover study was conducted to investigate whether the coadministration of zafirlukast would affect the pharmacokinetics of azithromycin, clarithromycin, or 14-hydroxyclarithromycin (14-OHC). Twelve healthy subjects (six males and six females) received single 500-mg doses of azithromycin and clarithromycin with and without zafirlukast given to a steady-state concentration. Blood was collected prior to all macrolide doses and for 3 and 10 days after each clarithromycin and azithromycin dose, respectively. Serum was assayed for azithromycin, clarithromycin, and 14-OHC concentrations by validated high-performance liquid chromatography assay systems. Data analyses were done by noncompartmental and nonparametric methods. Analysis of the patients indicated that the addition of steady-state concentrations of zafirlukast did not significantly alter the pharmacokinetic parameters of or overall exposure (based on the area under the concentration-time curve) to azithromycin, clarithromycin, and 14-OHC. While zafirlukast is a known inhibitor of CYP3A4, it does not appear to exert a clinically or statistically significant pharmacokinetic effect on azithromycin, clarithromycin, or 14-OHC.

scholarly journals Rifampin Reduces Concentrations of Trimethoprim and Sulfamethoxazole in Serum in Human Immunodeficiency Virus-Infected Patients

2001 ◽  
Vol 45 (11) ◽  
pp. 3238-3241 ◽  
Author(s):  
Esteban Ribera ◽  
Leonor Pou ◽  
Antoni Fernandez-Sola ◽  
Francisco Campos ◽  
Rosa M. Lopez ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
High Performance Liquid Chromatography ◽  
High Performance ◽  
Parent Drug ◽  
Time Curve ◽  
Once Daily ◽  
Concentration Time ◽  
Antituberculosis Treatment ◽  
Immunodeficiency Virus ◽  
Before And After

ABSTRACT To determine whether rifampin reduces concentrations of trimethoprim (TMP) and sulfamethoxazole (SMX) in serum of human immunodeficiency virus (HIV)-infected persons, levels of these agents were determined by high-performance liquid chromatography before and after more than 12 days of standard antituberculosis treatment for 10 patients who had been taking one double-strength tablet of co-trimoxazole once daily for more than 1 month. Statistically significant, 47 and 23% decreases in TMP and SMX mean areas under the concentration-time curve from 0 to 24 h (AUC0–24), respectively, were observed after administration of rifampin.N-Acetyl-SMX profiles without and with rifampin were similar. The steady-state AUC0–24 metabolite/parent drug ratio increased by 32% with rifampin administration. Our study shows that rifampin reduces profiles of TMP and SMX in serum of HIV-infected patients.

scholarly journals Pharmacokinetics of sparfloxacin and interaction with cisapride and sucralfate.

1997 ◽  
Vol 41 (8) ◽  
pp. 1668-1672 ◽  
Author(s):  
J A Zix ◽  
H F Geerdes-Fenge ◽  
M Rau ◽  
J Vöckler ◽  
K Borner ◽  
...  
Keyword(s):  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
Peak Concentration ◽  
High Performance ◽  
Random Order ◽  
Pharmacokinetic Parameters ◽  
Qtc Interval ◽  
Urinary Recovery ◽  
Time Curve ◽  
Concentration Time

In an open, randomized, triple crossover study, the effects of cisapride and sucralfate on the pharmacokinetics of sparfloxacin were assessed. Fifteen healthy volunteers received 400 mg of sparfloxacin as a single oral dose on day 0. In a random order, concomitant doses of 10 mg of cisapride three times daily from day -2 to day 2 and 1 g of sucralfate four times daily from day -2 to day 0 were administered. Sparfloxacin concentrations were measured by bioassay and high-performance liquid chromatography. Pharmacokinetic parameters for sparfloxacin alone were as follows (mean +/- standard deviation): maximum concentration of drug in serum (C(max)), 1.27 +/- 0.39 microg/ml; time to C(max) (T(max)), 4.1 +/- 1.9 h; area under the concentration-time curve (AUC), 35.0 +/- 9.7 microg x h/ml; mean residence time, 28.5 +/- 5.7 h; half-life (t1/2), 20 +/- 4 h; urinary recovery (UR x f), 11.0% +/- 2.7%; and metabolite-sparfloxacin ratio in urine, 2.6. For the cisapride group there was a significant decrease in the sparfloxacin T(max) (1.9 +/- 2.1 h) and a significant increase in C(max) (1.74 +/- 0.73 microg/ml). The QTc interval for patients receiving sparfloxacin and cisapride was prolonged by 7.7% compared to the QTc interval during medication-free periods. Significant differences in the values for the group receiving sucralfate compared to the values for the group receiving sparfloxacin alone were found: C(max), 0.77 +/- 0.31 microg/ml; AUC, 18.6 +/- 5.8 microg x h/ml; t1/2, 26 +/- 10 h; and UR x f, 5.8 +/- 1.8%. Concomitant adminstration of cisapride accelerates the absorption and increases the peak concentration of sparfloxacin without having a significant effect on the extent of bioavailability. Coadministration of sucralfate leads to a 44% decrease in the bioavailability of sparfloxacin.

scholarly journals Comparing Pharmacokinetics of Amoxicillin Given Twice or Three Times per Day to Children Older than 3 Months with Pneumonia

2003 ◽  
Vol 47 (3) ◽  
pp. 997-1001 ◽  
Author(s):  
Walter Fonseca ◽  
Kalle Hoppu ◽  
Luís C. Rey ◽  
João Amaral ◽  
Shamim Qazi
Keyword(s):  
High Performance ◽  
Dose Interval ◽  
World Health ◽  
Time Curve ◽  
Oral Amoxicillin ◽  
Concentration Time ◽  
Feasible Alternative ◽  
The Mean ◽  
Health Organization ◽  
Body Weight Dose

ABSTRACT For children with ambulatory pneumonia, the World Health Organization (WHO) recommends oral amoxicillin (15 mg/kg of body weight/dose) thrice daily (t.i.d.) or oral cotrimoxazole (4 mg of trimethoprim/kg/dose) twice daily (b.i.d.). The more frequent amoxicillin dosing may lead to compliance problems. To compare the pharmacokinetics and levels of amoxicillin in plasma in the current WHO acute respiratory infection recommendations with the 25-mg/kg/dose b.i.d. regimen, we performed a two-group parallel study of 66 children ages 3 to 59 months with pneumonia. Amoxicillin was given orally at 25 mg/kg/dose b.i.d. or 15 mg/kg/dose t.i.d. Amoxicillin concentrations were determined by high-performance liquid chromatography after the first dose on days 1 and 3. After the first dose on day 1, the mean area under the concentration-time curve (AUC) for amoxicillin after the 25-mg/kg dose was 54.7 versus 24.9 μg · h/ml after the 15-mg/kg dose. After the first dose on day 3, the mean AUC was 44.1 versus 28.5 μg · h/ml. All but two children had plasma amoxicillin concentrations above 0.5 μg/ml for >50% of the dose interval on both days. Six children on day 1 and five children on day 3 had concentrations above 1.0 μg/ml for <50% of the dose interval. On day 1, 16 of 27 children in the b.i.d. group and 11 of 26 children in the t.i.d. group had concentrations that were above 2.0 μg/ml for <50% of the dose interval, and on day 3, 18 of 31 children in the b.i.d. group and 8 of 31 children in the t.i.d. group had concentrations that were above 2.0 μg/ml for <50% of the dose interval. Amoxicillin b.i.d. is a feasible alternative for t.i.d. dosing. To lengthen the time above the MIC at higher concentration levels, a 30- to 40-mg/kg/dose b.i.d. should be considered instead of the 25 mg/kg/dose used in this study.

Modulation of Irinotecan Metabolism by Ketoconazole

2002 ◽  
Vol 20 (14) ◽  
pp. 3122-3129 ◽  
Author(s):  
Diederik F.S. Kehrer ◽  
Ron H.J. Mathijssen ◽  
Jaap Verweij ◽  
Peter de Bruijn ◽  
Alex Sparreboom
Keyword(s):  
Cancer Patients ◽  
High Performance ◽  
Advanced Colorectal Cancer ◽  
Enzyme Inhibitor ◽  
Cytochrome P450 3A4 ◽  
Time Curve ◽  
Simultaneous Treatment ◽  
Concentration Time ◽  
Irinotecan Dose

PURPOSE: Irinotecan (CPT-11) is a prodrug of SN-38 and has been registered for the treatment of advanced colorectal cancer. It is converted by the cytochrome P450 3A4 isozyme (CYP3A4) into several inactive metabolites, including 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino]-carbonyloxycamptothecin (APC). To investigate the role of CYP3A4 in irinotecan pharmacology, we evaluated the consequences of simultaneous treatment of irinotecan with a potent enzyme inhibitor, ketoconazole, in a group of cancer patients. PATIENTS AND METHODS: A total of seven assessable patients was treated in a randomized, cross-over design with irinotecan (350 mg/m2 intravenously for 90 minutes) given alone and followed 3 weeks later by irinotecan (100 mg/m2) in combination with ketoconazole (200 mg orally for 2 days) or vice versa. Serial plasma, urine, and feces samples were obtained up to 500 hours after dosing and analyzed for irinotecan, metabolites (7-ethyl-10-hydroxycamptothecin [SN-38], SN-38 glucuronide [SN-38G], and APC), and ketoconazole by high-performance liquid chromatography. RESULTS: With ketoconazole coadministration, the relative formation of APC was reduced by 87% (P = .002), whereas the relative exposure to the carboxylesterase-mediated SN-38 as expected on the basis of dose (area under the plasma concentration-time curve normalized to dose) was increased by 109% (P = .004). These metabolic alterations occurred without substantial changes in irinotecan clearance (P = .90) and formation of SN-38G (P = .93). CONCLUSION: Inhibition of CYP3A4 in cancer patients treated with irinotecan leads to significantly increased formation of SN-38. Simultaneous administration of various commonly prescribed inhibitors of CYP3A4 can potentially result in fatal outcomes, and up to four-fold reductions in irinotecan dose are indicated.

The Pharmacokinetics of Loratadine in Normal Geriatric Volunteers

1988 ◽  
Vol 16 (1) ◽  
pp. 50-60 ◽  
Author(s):  
J. Hilbert ◽  
V. Moritzen ◽  
A. Parks ◽  
E. Radwanski ◽  
G. Perentesis ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
High Performance ◽  
The Elderly ◽  
Maximum Plasma Concentration ◽  
Pharmacokinetic Analysis ◽  
Maximum Plasma ◽  
Open Label ◽  
Post Dose ◽  
Time Curve ◽  
Concentration Time

The pharmacokinetics of loratadine, a non-sedating anti-histamine, were studied in 12 normal geriatric volunteers. In an open label fashion, each volunteer received one 40 mg loratadine capsule. Blood was collected prior to and at specified times (up to 120 h) after dosing. Plasma loratadine concentrations were determined by a specific radioimmunoassay and those of an active metabolite, descarboethoxyloratadine, by high performance liquid chromatography. Concentrations of loratadine in the disposition phase were fitted to a biexponential equation and those of descarboethoxyloratadine to either a monoexponential or biexponential equation for pharmacokinetic analysis. Loratadine was rapidly absorbed, reaching a maximum plasma concentration of 50.5 ng/ml at 1.5 h after dosing. The disposition half-lives of loratadine in the distribution and elimination phases were 1.5 and 18.2 h, respectively. The area under the plasma concentration–time curve, was 146.7 h·ng/ml. Descarboethoxyloratadine had a maximum plasma concentration of 28.0 ng/ml at 2.9 h post-dose and an area under the concentration–time curve of 394.9 h·ng/ml. Its disposition half-lives in the distribution and elimination phases were 2.8 and 17.4 h, respectively. Comparison of these data with those from a previous study of loratadine in young adults showed no clear differences in the disposition half-lives between the two groups. The clearance of loratadine tends to be lower in the elderly, but inter-individual variation within each age group appears greater than any age effect.

Influence of Hypovolemia on the Pharmacokinetics and Electroencephalographic Effect of γ-Hydroxybutyrate in the Rat

2002 ◽  
Vol 97 (5) ◽  
pp. 1218-1226 ◽  
Author(s):  
Diederik K. Van Sassenbroeck ◽  
Peter De Paepe ◽  
Frans M. Belpaire ◽  
Paul A. Boon ◽  
Walter A. Buylaert
Keyword(s):  
Blood Pressure ◽  
High Performance ◽  
Compartment Model ◽  
Volume Of Distribution ◽  
Control Procedure ◽  
Time Data ◽  
Time Curve ◽  
Concentration Time ◽  
Gamma Hydroxybutyrate ◽  
Significant Difference

Background Hypovolemia alters the effect of propofol in the rat by influencing the pharmacokinetics and the end organ sensitivity. We now studied the effect of hypovolemia on the anesthetic gamma-hydroxybutyrate (GHB) because in contrast with propofol it increases blood pressure. Methods Thirty-two rats were randomly assigned to undergo moderate hypovolemia or a control procedure. Each rat received either an infusion of sodium-GHB (390 mg x kg(-1) x 5 min(-1)) or the same volume of an equimolar solution of sodium chloride (6.9%). Plasma samples were taken for GHB assay (high-performance liquid chromatography) and the electroencephalography and blood pressure values were recorded. A two-compartment model with Michaelis-Menten elimination was fitted to the concentration-time data and a sigmoid E(max) model to the electroencephalographic effect effect site concentration curve allowing the study of the end organ sensitivity. Results Plasma concentration-time curves and the total volume of distribution in hypovolemic and normovolemic rats were comparable with only small but significant differences in central volume of distribution and the intercompartmental clearance. There was no significant difference either in the distribution from the plasma to the brain (k(e0)) or in the end organ sensitivity (EC50 = 335 +/- 76 microg/ml in control vs. 341 +/- 89 microg/ml in hypovolemic rats). GHB temporarily increased mean arterial pressure in both groups, which cannot be explained by the sodium salt alone. Conclusions Hypovolemia does not influence the overall concentration-time curve of GHB and induces no changes in the electroencephalographic effect of GHB in the rat. This difference with propofol may be due to the fact that it increases blood pressure but also due to its different pharmacokinetic properties.

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