scholarly journals Voriconazole Increases while Itraconazole Decreases Plasma Meloxicam Concentrations

2008 ◽  
Vol 53 (2) ◽  
pp. 587-592 ◽  
Author(s):  
V. V. Hynninen ◽  
K. T. Olkkola ◽  
L. Bertilsson ◽  
K. J. Kurkinen ◽  
T. Korhonen ◽  
...  
Keyword(s):  
Peak Concentration ◽  
Plasma Concentrations ◽  
Cytochrome P450 2C9 ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Time Curve ◽  
Unbound Fraction ◽  
Control Phase ◽  
Concentration Time ◽  
The Mean ◽  
Plasma Concentration Time Curve

ABSTRACT This study investigated the effect of voriconazole, an inhibitor of cytochrome P450 2C9 (CYP2C9) and CYP3A4, and itraconazole, an inhibitor of CYP3A4, on the pharmacokinetics and pharmacodynamics of meloxicam. Twelve healthy volunteers in a crossover study ingested 15 mg of meloxicam without pretreatment (control), after voriconazole pretreatment, and after itraconazole pretreatment. The plasma concentrations of meloxicam, voriconazole, itraconazole, and thromboxane B2 (TxB2) generation were monitored. Compared to the control phase, voriconazole increased the mean area under the plasma concentration-time curve from 0 to 72 h (AUC0-72) of meloxicam by 47% (P < 0.001) and prolonged its mean half-life (t 1/2) by 51% (P < 0.01), without affecting its mean peak concentration (C max). In contrast, itraconazole decreased the mean AUC0-72 and C max of meloxicam by 37% (P < 0.001) and by 64% (P < 0.001), respectively, and prolonged its t 1/2 and time to C max. The plasma protein unbound fraction of meloxicam was unchanged by voriconazole and itraconazole. Lowered plasma meloxicam concentrations during the itraconazole phase were associated with decreased pharmacodymic effects of meloxicam, as observed by weaker inhibition of TxB2 synthesis compared to the control and voriconazole phases. Voriconazole increases plasma concentrations of meloxicam, whereas itraconazole, unexpectedly, decreases plasma meloxicam concentrations, possibly by impairing its absorption.

Exposure to Retinoic Acids in Non-Pregnant Women Following High Vitamin A Intake with a Liver Meal

2005 ◽  
Vol 75 (3) ◽  
pp. 187-194 ◽  
Author(s):  
Hartmann ◽  
Brørs ◽  
Bock ◽  
Blomhoff ◽  
Bausch ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Vitamin A ◽  
Safety Concern ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Pregnant Female ◽  
Time Curve ◽  
High Vitamin ◽  
Concentration Time ◽  
Plasma Concentration Time Curve

Animal liver is a rich source of vitamin A. Due to retinoic acid (RA) metabolites, vitamin A has a teratogenic potential and women are generally advised to avoid or to limit the consumption of liver during pregnancy. In a recent study in non-pregnant female volunteers following single and repeated doses of up to 30,000 IU/day of vitamin A as a supplement, the plasma concentration time curve of all-trans RA acid showed a diurnal-like profile. But, the overall exposure (AUC24h) remained essentially unaltered whereas AUC24h increased linearly with dose for 13-cis and 13-cis-4-oxo RA. The current study in non-pregnant female volunteers showed that a single high vitamin A intake with a liver meal (up to 120,000 IU) exhibited a similar diurnal-like plasma concentration time curve for all-trans RA and its overall exposure remained also unaltered, despite a temporary two-fold increase in peak plasma concentration. Concentrations of 13-cis and 13-cis-4-oxo RA increased several-fold after a liver meal, and exposure (AUC24h) increased three- to five-fold. Pooling our results with data in the literature revealed a linear relation between the mean AUC24h of 13-cis and 13-cis-4-oxo RA and vitamin A intake with liver. Metabolism to all-trans RA of vitamin A with liver seems not to be of safety concern. However, the observed increase of plasma concentrations and the dose-dependent increase in exposure to 13-cis and 13-cis-4-oxo RA support the current safety recommendations on vitamin A intake and suggest that women should be cautious regarding their consumption of liver-containing meals during pregnancy.

Interaction of Metoprolol, Propranolol and Atenolol with Cimetidine

1982 ◽  
Vol 63 (s8) ◽  
pp. 451s-453s ◽  
Author(s):  
W. Kirch ◽  
H. Spahn ◽  
H. Köhler ◽  
E. Mutschler
Keyword(s):  
Plasma Concentration ◽  
Healthy Volunteers ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Concurrent Administration ◽  
Time Curve ◽  
Concentration Time ◽  
Plasma Concentration Time Curve

1. Pharmacokinetics of metoprolol, propranolol and atenolol were investigated in six healthy volunteers after 7 days of oral monotherapy with these drugs and after 7 days concurrent administration, with each of these β-adrenoceptor antagonists with cimetidine. 2. Cimetidine did not interact with atenolol, whereas mean peak plasma concentrations of metoprolol were increased by 70%, and those of propranolol by 95% with concurrent administration of cimetidine (P < 0.05). 3. The area under the plasma concentration-time curve for propranolol and metoprolol was similarly increased (P < 0.05).

scholarly journals Colistin Methanesulfonate and Colistin Pharmacokinetics in Critically Ill Patients Receiving Continuous Venovenous Hemodiafiltration

2012 ◽  
Vol 57 (1) ◽  
pp. 668-671 ◽  
Author(s):  
Matti Karvanen ◽  
Diamantis Plachouras ◽  
Lena E. Friberg ◽  
Elisabeth Paramythiotou ◽  
Evangelos Papadomichelakis ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Total Clearance ◽  
Time Curve ◽  
Unbound Fraction ◽  
Continuous Venovenous Hemodiafiltration ◽  
Concentration Time ◽  
Fourth Dose ◽  
The Mean ◽  
Colistin Methanesulfonate ◽  
Mean Concentration

ABSTRACTThis report describes the pharmacokinetics of colistin methanesulfonate (CMS) and colistin in five intensive care unit patients receiving continuous venovenous hemodiafiltration. For CMS, the mean maximum concentration of drug in plasma (Cmax) after the fourth dose was 6.92 mg/liter and total clearance (CL) 8.23 liters/h. For colistin, the mean concentration was 0.92 mg/liter and CL/metabolized fraction (fm) 18.91 liters/h. Colistin concentrations were below the current MIC breakpoints, and the area under the concentration-time curve for the free, unbound fraction of the drug over 24 h in the steady state divided by the MIC (fAUC/MIC) was lower than recommended, suggesting that a dosage regimen of 160 mg CMS every 8 h (q8h) is inadequate.

scholarly journals Switch from Enfuvirtide to Raltegravir Lowers Plasma Concentrations of Darunavir and Tipranavir: a Pharmacokinetic Substudy of the EASIER-ANRS 138 Trial

2011 ◽  
Vol 55 (7) ◽  
pp. 3613-3615 ◽  
Author(s):  
Lauriane Goldwirt ◽  
Joséphine Braun ◽  
Nathalie de Castro ◽  
Isabelle Charreau ◽  
Aurélie Barrail-Tran ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Human Immunodeficiency Virus ◽  
Steady State ◽  
Geometric Mean ◽  
Plasma Concentrations ◽  
Time Curve ◽  
Concentration Time ◽  
Background Regimen ◽  
Immunodeficiency Virus ◽  
Plasma Concentration Time Curve

ABSTRACTWe compared tipranavir and darunavir concentrations measured at steady state in 20 human immunodeficiency virus (HIV)-infected patients enrolled in the EASIER-ANRS 138 clinical trial who switched from enfuvirtide to raltegravir while maintaining the same background regimen. The geometric mean ratios of the observed predose concentration (Ctrough), maximum concentration of drug observed in plasma (Cmax), and area under the plasma concentration-time curve (AUC) before (day 0) and after (week 24) the switch were 0.49, 0.76, and 0.67 and 0.82, 0.68, and 0.64 for tipranavir and darunavir, respectively. The virologic consequences of these drug interactions have yet to be determined.

scholarly journals Artemether Bioavailability after Oral or Intramuscular Administration in Uncomplicated Falciparum Malaria

2003 ◽  
Vol 47 (12) ◽  
pp. 3795-3798 ◽  
Author(s):  
Kamolrat Silamut ◽  
Paul N. Newton ◽  
Paktiya Teja-Isavadharm ◽  
Yupin Suputtamongkol ◽  
Duangsuda Siriyanonda ◽  
...  
Keyword(s):  
Oral Administration ◽  
Acute Phase ◽  
Peak Concentration ◽  
Antimalarial Activity ◽  
Acute Illness ◽  
Intramuscular Administration ◽  
Time Curve ◽  
Convalescent Phase ◽  
Concentration Time ◽  
Plasma Concentration Time Curve

ABSTRACT The antimalarial activity of artemether following oral or intramuscular administration in the plasma of 15 adults with acute uncomplicated Plasmodium falciparum malaria was measured by bioassay. The peak concentrations in plasma following oral administration were higher in patients with acute illness (median, 1,905 mmol of dihydroartemisinin [DHA] equivalents per liter; range, 955 to 3,358 mmol of DHA equivalents per liter) than in patients in the convalescent phase (median, 955 mmol of DHA equivalents per liter; range, 576 to 1,363 mmol of DHA equivalents per liter), and clearance (CL/F) was lower in patients in the acute phase (1.11 liters/kg/h; range, 0.21 to 3.08 liters/kg/h) than in patients in the convalescent phase (median, 2.76 liters/kg/h; range, 1.56 to 5.74 liters/kg/h) (P ≤ 0.008). Antimalarial activity in terms of the peak concentration in plasma (C max) after oral administration was a median of 16 times higher than that after intramuscular administration. The ratio of the area under the plasma concentration-time curve during the first 24 h (AUC0-24) after oral administration of artemether to the AUC0-24 after intramuscular administration was a median of 3.3 (range, 1 to 11) (P = 0.0001). In the acute phase, the time to C max was significantly shorter after oral administration (median, 1 h; range, 0.5 to 3.0 h) than after intramuscular administration (median, 8 h; range, 4 to 24 h) (P = 0.001). Intramuscular artemether is absorbed very slowly in patients with acute malaria.

scholarly journals Relationship between Plasma Concentrations of Afatinib and the Onset of Diarrhea in Patients with Non-Small Cell Lung Cancer

Biology ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1054
Author(s):  
Hayato Yokota ◽  
Kazuhiro Sato ◽  
Sho Sakamoto ◽  
Yuji Okuda ◽  
Mariko Asano ◽  
...  
Keyword(s):  
Single Point ◽  
Plasma Concentrations ◽  
Small Cell ◽  
Therapeutic Drug ◽  
Small Cell Lung ◽  
Time Curve ◽  
Concentration Time ◽  
Kaplan Meier ◽  
Daily Dose ◽  
Plasma Concentration Time Curve

We evaluated the area under the plasma concentration–time curve (AUC) of afatinib required to avoid the onset of grade 2 or higher diarrhea. The C0 and AUC0–24 of afatinib were significant higher in patients with grade 2 diarrhea than in those with grade 0–1 diarrhea. The areas under the receiver operator curves were 0.795 with the highest sensitivity (89%) and specificity (74%) at an AUC0–24 threshold of 823.5 ng·h/mL, and 0.754 with the highest sensitivity (89%) and specificity (74%) at a C0 threshold of 28.5 ng/mL. In Kaplan–Meier analysis based on these cut-off AUC0–24 and C0 values, the median time to the incidence of grade 2 diarrhea was 16 days. The predicted AUC0–24 of afatinib from the single point of C6 showed the highest correlation with the measured AUC0–24 (r2 = 0.840); however, a significant correlation between the AUC0–24 and C0 was also observed (r2 = 0.761). C0 could be used as a marker of therapeutic drug monitoring because afatinib C0 was related to AUC0–24. Therefore, afatinib C0 should be monitored on day 8 after beginning therapy, and the daily dose of afatinib should be adjusted as an index with a cut-off value of 28.5 ng/mL.

scholarly journals Repeated Administration of High-Dose Intermittent Rifapentine Reduces Rifapentine and Moxifloxacin Plasma Concentrations

2008 ◽  
Vol 52 (11) ◽  
pp. 4037-4042 ◽  
Author(s):  
Kelly Dooley ◽  
Charles Flexner ◽  
Judith Hackman ◽  
Charles A. Peloquin ◽  
Eric Nuermberger ◽  
...  
Keyword(s):  
Phase I ◽  
Adverse Reactions ◽  
Plasma Concentrations ◽  
Repeated Administration ◽  
Hypersensitivity Syndrome ◽  
Sequential Design ◽  
High Dose ◽  
Time Curve ◽  
Concentration Time ◽  
The Mean

ABSTRACT Moxifloxacin- and rifapentine-based regimens are under investigation for the treatment of tuberculosis. However, rifapentine may induce enzymes that metabolize moxifloxacin, resulting in decreased moxifloxacin concentrations. In this phase I, two-period, sequential-design study, 13 subjects received 400 mg moxifloxacin daily for 4 days followed by daily moxifloxacin coadministered with 900 mg rifapentine thrice weekly. Pharmacokinetic analyses were performed after the 4th and 19th doses of moxifloxacin and after the 1st and 7th doses of rifapentine. For moxifloxacin, the mean area under the concentration-time curve from 0 to 24 h (AUC0-24) decreased by 17.2% (P = 0.0006) when the drug was coadministered with rifapentine, and the mean half-life (t 1/2) decreased from 11.1 to 8.9 h (P = 0.0033). For rifapentine, the mean AUC0-48 after seven thrice-weekly doses decreased by 20.3% (P = 0.0035) compared to the AUC0-48 after the first dose, and the mean t 1/2 decreased from 18.5 to 14.8 h (P = 0.0004). The AUC0-48 for the 25-desacetyl-rifapentine metabolite diminished 21%. Two days after completing the study drugs, one subject developed a fever and hepatitis, and another developed a flu-like illness with a rash. In conclusion, rifapentine modestly reduced moxifloxacin concentrations. Changes consistent with rifapentine autoinduction of metabolism were seen. Adverse reactions in two subjects may have represented rifamycin hypersensitivity syndrome, although some features were atypical.

scholarly journals Validation of Heel Stick Microsampling To Optimize Micafungin Doses in Neonates and Young Infants

2018 ◽  
Vol 62 (10) ◽  
Author(s):  
Cinzia Auriti ◽  
Bianca Maria Goffredo ◽  
Maria Paola Ronchetti ◽  
Fiammetta Piersigilli ◽  
Sara Cairoli ◽  
...  
Keyword(s):  
Dose Adjustment ◽  
Plasma Concentrations ◽  
Therapeutic Drug ◽  
Strongly Correlated ◽  
Time Curve ◽  
Young Infants ◽  
Concentration Time ◽  
Critically Ill Neonates ◽  
The Mean ◽  
Neonates And Infants

ABSTRACT Major gaps exist in our knowledge of antimicrobial pharmacokinetics in critically ill neonates and infants that require validated microsampling and bioanalysis methods to support therapeutic drug monitoring. We compared serially collected intravenous (i.v.) and heel stick capillary (HSC)-sampled plasma concentrations of micafungin (8 mg/kg) in eight infants born preterm with systemic candidiasis. The mean (standard deviation) micafungin area under the plasma concentration-time curve to infinity (AUCinf) was 316 (65.0) h · mg/liter based on HSC concentrations that strongly correlated (R2 = 0.92) with i.v. values to support dose adjustment.

scholarly journals Comparison of Plasma, Epithelial Lining Fluid, and Alveolar Macrophage Concentrations of Solithromycin (CEM-101) in Healthy Adult Subjects

2012 ◽  
Vol 56 (10) ◽  
pp. 5076-5081 ◽  
Author(s):  
Keith A. Rodvold ◽  
Mark H. Gotfried ◽  
J. Gordon Still ◽  
Kay Clark ◽  
Prabhavathi Fernandes
Keyword(s):  
Steady State ◽  
High Performance ◽  
Healthy Adult ◽  
Plasma Concentrations ◽  
Epithelial Lining ◽  
Time Curve ◽  
Epithelial Lining Fluid ◽  
Once Daily ◽  
Drug Concentrations ◽  
The Mean

ABSTRACTThe steady-state concentrations of solithromycin in plasma were compared with concomitant concentrations in epithelial lining fluid (ELF) and alveolar macrophages (AM) obtained from intrapulmonary samples during bronchoscopy and bronchoalveolar lavage (BAL) in 30 healthy adult subjects. Subjects received oral solithromycin at 400 mg once daily for five consecutive days. Bronchoscopy and BAL were carried out once in each subject at either 3, 6, 9, 12, or 24 h after the last administered dose of solithromycin. Drug concentrations in plasma, ELF, and AM were assayed by a high-performance liquid chromatography-tandem mass spectrometry method. Solithromycin was concentrated extensively in ELF (range of mean [± standard deviation] concentrations, 1.02 ± 0.83 to 7.58 ± 6.69 mg/liter) and AM (25.9 ± 20.3 to 101.7 ± 52.6 mg/liter) in comparison with simultaneous plasma concentrations (0.086 ± 0.070 to 0.730 ± 0.692 mg/liter). The values for the area under the concentration-time curve from 0 to 24 h (AUC0–24values) based on mean and median ELF concentrations were 80.3 and 63.2 mg · h/liter, respectively. The ratio of ELF to plasma concentrations based on the mean and median AUC0–24values were 10.3 and 10.0, respectively. The AUC0–24values based on mean and median concentrations in AM were 1,498 and 1,282 mg · h/L, respectively. The ratio of AM to plasma concentrations based on the mean and median AUC0–24values were 193 and 202, respectively. Once-daily oral dosing of solithromycin at 400 mg produced steady-state concentrations that were significantly (P< 0.05) higher in ELF (2.4 to 28.6 times) and AM (44 to 515 times) than simultaneous plasma concentrations throughout the 24-h period after 5 days of solithromycin administration.

scholarly journals Pharmacokinetics and pharmacodynamics of two multiple-dose piperacillin-tazobactam regimens.

1997 ◽  
Vol 41 (11) ◽  
pp. 2511-2517 ◽  
Author(s):  
D J Occhipinti ◽  
S L Pendland ◽  
L L Schoonover ◽  
E B Rypins ◽  
L H Danziger ◽  
...  
Keyword(s):  
Bactericidal Activity ◽  
Dosage Regimen ◽  
Multiple Dose ◽  
Antimicrobial Agents ◽  
Plasma Concentrations ◽  
Culture Collection ◽  
Beta Lactam ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Time Curve ◽  
Bacteriological Response

The pharmacokinetics and pharmacodynamics of two multiple-dose regimens of piperacillin-tazobactam (3.375 g every 6 h and 4.5 g every 8 h) were evaluated at steady state for 12 healthy adult volunteers. Inhibitory and bactericidal activities for the two regimens were determined with five American Type Culture Collection (ATCC) organisms (Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Bacteroides fragilis). The percentage of time that plasma concentrations remained above the MIC (T > MIC) for each organism and dosage regimen was calculated. Areas under the inhibitory (AUIC0-24) and bactericidal activity (AUBC0-24) curves were calculated with the trapezoidal rule by using the reciprocal of the inhibitory and bactericidal titers determined for each dosage regimen. In order to assess the validity of predicted measures of bactericidal (AUC0-24/MBC) and inhibitory (AUC0-24/MIC) activity to determine bacteriological response to beta-lactam antimicrobial agents, AUC0-24/MBC and AUC0-24/MIC values were compared with measured AUBC0-24 and AUIC0-24 values. Total body clearance values were equivalent for piperacillin (183.96 +/- 22.66 versus 181.72 +/- 19.54 ml/min/1.73 m2, P > 0.05) and tazobactam (184.71 +/- 19.89 versus 184.87 +/- 18.35 ml/min/1.73 m2, P > 0.05) following the administration of the 3.375-g-every-6-h and 4.5-g-every-8-h dosages, respectively. Comparison of area under the plasma concentration-time curve (AUC0-24) for piperacillin (967.74 +/- 135.56 microg x h/ml versus 978.88 +/- 140.96 microg x h/ml) and tazobactam (120.14 +/- 15.78 microg x h/ml versus 120.01 +/- 16.22 microg x h/ml) revealed no significant differences (P > 0.05) between the 3.375-g-every-6-h and 4.5-g-every-8-h regimens, respectively. Both regimens provided T > MIC values of > 60% for all organisms tested. Measured values of bactericidal (AUBC) and inhibitory (AUIC) activity were significantly different (P < 0.05) from predicted values (AUC0-24/MBC and AUC0-24/MIC) for all organisms studied with the exception of the bactericidal activity for P. aeruginosa and S. aureus. Additionally, ATCC organisms possessing the same MICs and MBCs exhibited great differences in measured AUBC0-24 and AUIC0-24 values. Reasons for this difference may be inherent differences in organism specific susceptibility.

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