Effect of Terbinafine on Theophylline Pharmacokinetics in Healthy Volunteers

1998 ◽  
Vol 42 (3) ◽  
pp. 695-697 ◽  
Author(s):  
Eric F. Trépanier ◽  
Anne N. Nafziger ◽  
Guy W. Amsden
Keyword(s):  
Healthy Volunteers ◽  
Multiple Dose ◽  
Treatment Phase ◽  
Pharmacokinetic Parameters ◽  
Noncompartmental Analysis ◽  
Open Label ◽  
Time Curve ◽  
Blood Samples ◽  
Concentration Time ◽  
Randomized Crossover Study

ABSTRACT Twelve healthy volunteers were enrolled in an open-label, randomized, crossover study. Subjects received single doses of theophylline (5 mg/kg) with and without multiple-dose terbinafine, and 11 blood samples were collected over 24 h. The study phases were separated by a 4-week washout period. Theophylline serum data were modeled via noncompartmental analysis. When the control phase (i.e., no terbinafine) was compared to the treatment phase (terbinafine), theophylline exposure (the area under the serum concentration-time curve from time zero to infinity) increased by 16% (P= 0.03), oral clearance decreased by 14% (P = 0.04), and half-life increased by 24% (P = 0.002). No significant changes in other theophylline pharmacokinetic parameters were evident.

Lack of Effect of Ginkgo biloba on Voriconazole Pharmacokinetics in Chinese Volunteers Identified as CYP2C19 Poor and Extensive Metabolizers

2009 ◽  
Vol 43 (4) ◽  
pp. 726-731 ◽  
Author(s):  
He-Ping Lei ◽  
Guo Wang ◽  
Lian-Sheng Wang ◽  
Dong-sheng Ou-yang ◽  
Hao Chen ◽  
...  
Keyword(s):  
Single Dose ◽  
Ginkgo Biloba ◽  
Poor Metabolizers ◽  
Pharmacokinetic Parameters ◽  
Extensive Metabolizers ◽  
Herbal Supplements ◽  
Time Curve ◽  
Concentration Time ◽  
Apparent Clearance ◽  
Randomized Crossover Study

Background: Ginkgo biloba is one of the most popular herbal supplements in the world. The supplement has been shown to induce the enzymatic activity of CYP2C19, the main cytochrome P450 isozyme involved in voriconazole metabolism. Because this enzyme exhibits genetic polymorphism, the inductive effect was expected to be modulated by the CYP2C19 metabolizer status. Objective: To examine the possible effects of Ginkgo biloba as an inducer of CYP2C19 on single-dose pharmacokinetics of voriconazole in Chinese volunteers genotyped as either CVP2C19 extensive or poor metabolizers. Methods: Fourteen healthy, nonsmoking volunteers–7 CYP2C19 extensive metabolizers (2C19*1/2C19*1) and 7 poor metabolizers (2C19*2/2C19*2)–were selected to participate in this study. Pharmacokinetics of oral voriconazole 200 mg after administration of Ginkgo biloba 120 mg twice daily for 12 days were determined for up to 24 hours by liquid chromatography–electrospray tandem mass spectrometry in a 2-phase randomized crossover study with 4-week washout between phases. Results: For extensive metabolizers, the median value for voriconazole area under the plasma concentration–time curve from zero to infinity (AUC0-00) was 5.17 μg•h/mL after administration of voriconazole alone and 4.28 μg•/mL after voriconazole with Ginkgo biloba (p > 0.05). The other pharmacokinetic parameters of voriconazole such as AUC0-24, time to reach maximum concentration, half-life, and apparent clearance also did not change significantly for extensive metabolizers in the presence of Ginkgo biloba. Pharmacokinetic parameters followed a similar pattern for poor metabolizers. Conclusions: The results suggest that 12 days of treatment with Ginkgo biloba did not significantly alter the single-dose pharmacokinetics of voriconazole in either CYP2C19 extensive or poor metabolizers. Therefore, the pharmacokinetic interactions between voriconazole and Ginkgo biloba may have limited clinical significance.

Pharmacokinetics and Safety of Coadministered Oseltamivir and Rimantadine in Healthy Volunteers: An Open-Label, Multiple-Dose, Randomized, Crossover Study

2012 ◽  
Vol 52 (8) ◽  
pp. 1255-1264 ◽  
Author(s):  
Georgina Cirrincione-Dall ◽  
Barbara J. Brennan ◽  
Rosa M. Ballester-Sanchis ◽  
Mercidita T. Navarro ◽  
Brian E. Davies
Keyword(s):  
Crossover Study ◽  
Healthy Volunteers ◽  
Multiple Dose ◽  
Open Label ◽  
Randomized Crossover Study

scholarly journals P78 Pharmacokinetics of intravenous and intranasal nalbuphine in infants

2019 ◽  
Vol 104 (6) ◽  
pp. e49.2-e49
Author(s):  
M Pfiffner ◽  
V Gotta ◽  
E Berger-Olah ◽  
M Pfister ◽  
P Vonbach
Keyword(s):  
Maximum Concentration ◽  
Opioid Analgesic ◽  
Wilcoxon Test ◽  
Noncompartmental Analysis ◽  
Open Label ◽  
Post Dose ◽  
Time Curve ◽  
Acute Setting ◽  
Non Invasive ◽  
Concentration Time

BackgroundNalbuphine is a mixed agonist-antagonist opioid analgesic agent frequently used in paediatrics, and licensed for parenteral use only. Intranasal delivery could be a safe, effective and non-invasive alternative, especially in infants in the acute setting. However, pharmacokinetic (PK) data for this route of administration is completely lacking. The aim of this study was to assess PK of nalbuphine in infants 1–3 months after single intravenous (0.05 mg/kg) and intranasal (0.1 mg/kg) application, respectively.MethodsWe conducted a prospective, single centre, open-label pharmacokinetic study in infants 1–3 months undergoing sepsis workup in the emergency unit. Included infants received alternating nalbuphine as 0.05 mg/kg intravenous bolus or as 0.1 mg/kg intranasal spray. PK samples were taken at 3 pre-defined time points (15, 30 and max. 240 min post-dose before discharge). Area under the concentration-time curve (AUC0-Tlast, and AUC0-infinity for i.v.) was calculated using noncompartmental analysis and was compared between groups using Wilcoxon test. Further parameters derived included maximum concentration (Cmax), time of maximum concentration (Tmax for i.n.) and terminal half-life (t1/2).ResultsA total of 31 patients were included in the analysis. Median age was 55 days [interquartile range 38–63] in the intranasal (N=20) and 42 [37–76] days in the iv group (N=11). Median AUC0-Tlast was 7.6 (5.4–10.4) mcg*h/L following intranasal versus 7.9 (6.0–14.7) mcg*h/L for iv administration (p=0.46). AUC0-Tlast (i.v.) covered 80 [68–83]% of AUC0-infinity. Median Cmax was 4.5 [3.5–5.6] mcg/L (i.n.) versus 6.5 [5.3–15.9] mcg/L (i.v.) (p=0.014), t1/22.4 [1.3–2.8] h (i.n.) versus 1.3 [1.1–1.5] h (i.v.) (p=0.021). Tmax occurred 37 [32–65] min after intranasal administration.ConclusionThis first PK study of intranasal nalbuphine in infants suggests that 0.1 mg/kg i.n. dosing provides similar exposure as 0.05 mg/kg i.v. in infants in terms of AUC, and hence intranasal bioavailability close to 50%.Disclosure(s)Nothing to disclose

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 Induction of theophylline clearance by rifampin and rifabutin in healthy male volunteers.

1996 ◽  
Vol 40 (8) ◽  
pp. 1866-1869 ◽  
Author(s):  
J G Gillum ◽  
J M Sesler ◽  
V L Bruzzese ◽  
D S Israel ◽  
R E Polk
Keyword(s):  
Treatment Phase ◽  
Pharmacokinetic Parameters ◽  
Theophylline Clearance ◽  
Healthy Male ◽  
Time Curve ◽  
Concentration Time ◽  
Male Volunteers ◽  
Hepatic Microsomal Enzyme ◽  
The Mean ◽  
To Receive

Rifampin and rifabutin induce the metabolism of many drugs, which may result in subtherapeutic concentrations and failure of therapy. However, differences between rifabutin and rifampin in potency of induction, and the specific enzymes which are altered, are not clear. This study, involving 12 adult male volunteers, compared the effects of 14-day courses of rifampin and rifabutin on clearance of theophylline, a substrate for the hepatic microsomal enzyme CYP1A2. Subjects were given oral theophylline solution (5 mg/kg of body weight) on day 1 and then randomized to receive daily rifampin (300 mg) or rifabutin (300 mg) on days 3 to 16. Theophylline was readministered as described above on day 15. The first treatment sequence was followed by a 2-week washout period; subjects then received the alternative treatment. Theophylline concentrations were determined for 46 h after each dose, and pharmacokinetic parameters were determined. One subject developed flu-like symptoms while taking rifabutin and withdrew voluntarily. Results from the remaining 11 subjects are reported. Compared with the baseline, the mean area under the concentration-time curve (AUC) (+/- standard deviation) for theophylline declined significantly following rifampin treatment (from 140 +/- 37 to 100 +/- 24 micrograms . h/ml, P <0.001); there was no significant change following rifabutin treatment (136 +/- 48 to 128 +/- 45 micrograms.h/ml). Baseline theophylline AUCs before each treatment phase were not different. A comparison of equal doses of rifampin and rifabutin administered to healthy volunteers for 2 weeks indicates that induction of CYP1A2, as measured by theophylline clearance, is significantly less following rifabutin treatment than it is following rifampin treatment. However, the relative induction potency for other metabolic enzymes remains to be investigated.

scholarly journals Pharmacokinetic Study of Tenofovir Disoproxil Fumarate Combined with Rifampin in Healthy Volunteers

2005 ◽  
Vol 49 (2) ◽  
pp. 680-684 ◽  
Author(s):  
J. A. H. Droste ◽  
C. P. W. G. M. Verweij-van Wissen ◽  
B. P. Kearney ◽  
R. Buffels ◽  
P. J. vanHorssen ◽  
...  
Keyword(s):  
Tenofovir Disoproxil Fumarate ◽  
Multiple Dose ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Data ◽  
Open Label ◽  
Time Curve ◽  
Simultaneous Treatment ◽  
Minimum Concentration ◽  
Period 2 ◽  
Tenofovir Df

ABSTRACT Tenofovir disoproxil fumarate (tenofovir DF) was studied in combination with rifampin in 24 healthy subjects in a multiple-dose, open-label, single-group, two-period study. All subjects were given tenofovir DF at 300 mg once a day (QD) from days 1 to 10 (period 1). From days 11 to 20 the subjects received tenofovir DF at 300 mg combined with rifampin at 600 mg QD (period 2). The multiple-dose pharmacokinetics of tenofovir (day 10 and 20) and rifampin (day 20) were assessed. The drug-related adverse events (AEs) experienced during this study were mostly mild. Only one grade 3 AE possibly or probably related to the treatment (raised liver enzyme levels) occurred during period 2; the subject was withdrawn from the study. Pharmacokinetic data for 23 subjects were thus evaluable. Point estimates for the mean ratios of tenofovir with rifampin versus tenofovir alone for the area under the concentration-time curve from time zero to 24 h (AUC0-24), the maximum concentration of drug in plasma (C max), and the minimum concentration of drug in plasma (C min) were 0.88, 0.84, and 0.85, respectively. The 90% classical confidence intervals for AUC0-24, C max, and C min were 0.84 to 0.92, 0.78 to 0.90, and 0.80 to 0.91, respectively, thus suggesting pharmacokinetic equivalence. Similarly, coadministration of rifampin and tenofovir DF did not result in changes in the values of the tenofovir pharmacokinetic parameters. For rifampin, the values of the pharmacokinetic parameters found in this study were comparable to those found in the literature, indicating that tenofovir DF has no effect on the pharmacokinetics of rifampin. In conclusion, adaptation of either the rifampin or the tenofovir DF dose for the simultaneous treatment of tuberculosis and human immunodeficiency virus (HIV) infection in HIV-infected patients is probably not required.

scholarly journals The Bioavailability and Pharmacokinetics of Silymarin SMEDDS Formulation Study in Healthy Thai Volunteers

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Chuleegone Sornsuvit ◽  
Darunee Hongwiset ◽  
Songwut Yotsawimonwat ◽  
Manatchaya Toonkum ◽  
Satawat Thongsawat ◽  
...  
Keyword(s):  
Single Dose ◽  
Healthy Volunteers ◽  
Pharmacokinetic Study ◽  
Oral Bioavailability ◽  
Pharmacokinetic Parameters ◽  
Open Label ◽  
Blood Samples ◽  
Rapid Absorption ◽  
The Mean

The present study aimed to determine the pharmacokinetic parameters and bioavailability of silymarin 140 mg SMEDDS formulation. An open-label, single-dose pharmacokinetic study was conducted. Twelve healthy volunteers were included in the study. After the volunteers had fasted overnight for 10 h, a single-dose generic silymarin 140 mg SMEDDS soft capsule was administered. Then 10 ml blood samples were taken at 0.0, 0.25, 0.50, 0.75, 1.0, 1.33, 1.67, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 10.0, and 12.0 h. The plasma silybin concentrations were analyzed using validated LC-MS/MS. The pharmacokinetic parameters were analyzed and calculated. The pharmacokinetic parameters were calculated after silymarin had been administered as a single capsule. The mean (range) Cmax was 812.43 (259.47–1505.47) ng/ml at 0.80 (0.25–1.67) h (tmax). The mean (range) AUC0-t and AUC0-inf were 658.80 (268.29–1045.01) ng.h/ml and 676.98 (274.10–1050.96) ng.h/ml, respectively. The mean ke and t1/2 were 0.5386 h-1 and 1.91 h, respectively. The silymarin SMEDDS formulation soft capsule showed rapid absorption and high oral bioavailability.

scholarly journals Comparative Assessment of Tedizolid Pharmacokinetics and Tissue Penetration between Diabetic Patients with Wound Infections and Healthy Volunteers via In Vivo Microdialysis

2017 ◽  
Vol 62 (1) ◽  
Author(s):  
Sean M. Stainton ◽  
Marguerite L. Monogue ◽  
Arlinda Baummer-Carr ◽  
Ashley K. Shepard ◽  
James F. Nugent ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Subcutaneous Tissue ◽  
Extracellular Fluid ◽  
Pharmacokinetic Parameters ◽  
Diabetic Patients ◽  
Tissue Penetration ◽  
Time Curve ◽  
Dosing Interval ◽  
Concentration Time

ABSTRACT Herein, we present pharmacokinetic and tissue penetration data for oral tedizolid in hospitalized patients with diabetic foot infections (DFI) compared with healthy volunteers. Participants received oral tedizolid phosphate 200 mg every 24 h for 3 doses to achieve steady state. A microdialysis catheter was inserted into the subcutaneous tissue near the margin of the wound for patients or into thigh tissue of volunteers. Following the third dose, 12 blood and 14 dialysate fluid samples were collected over 24 h to characterize tedizolid concentrations in plasma and interstitial extracellular fluid of soft tissue. Mean ± standard deviation (SD) tedizolid pharmacokinetic parameters in plasma for patients compared with volunteers, respectively, were as follows: maximum concentration (C max), 1.5 ± 0.5 versus 2.7 ± 1.1 mg/liter (P = 0.005); time to C max (T max) (median [range]), 5.9 (1.2 to 8.0) versus 2.5 (2.0 to 3.0 h) (P = 0.003); half-life (t1/2), 9.1 ± 3.6 versus 8.9 ± 2.2 h (P = 0.932); and plasma area under the concentration-time curve for the dosing interval (AUC p ), 18.5 ± 9.7 versus 28.7 ± 9.6 mg · h/liter (P = 0.004). The tissue area under the concentration-time curve (AUC t ) for the dosing interval was 3.4 ± 1.5 versus 5.2 ± 1.6 mg · h/liter (P = 0.075). Tissue penetration median (range) was 1.1 (0.3 to 1.6) versus 0.8 (0.7 to 1.0) (P = 0.351). Despite lower plasma C max and delayed T max values for patients with DFI relative to healthy volunteers, the penetration into and exposure to tissue were similar. Based on available pharmacodynamic thresholds for tedizolid, the plasma and tissue exposures using the oral 200 mg once-daily regimen are suitable for further study in treatment of DFI.

scholarly journals Effect of a Nutritional Supplement on Posaconazole Pharmacokinetics following Oral Administration to Healthy Volunteers

2006 ◽  
Vol 50 (5) ◽  
pp. 1881-1883 ◽  
Author(s):  
Angela Sansone-Parsons ◽  
Gopal Krishna ◽  
Angela Calzetta ◽  
David Wexler ◽  
Bhavna Kantesaria ◽  
...  
Keyword(s):  
Oral Administration ◽  
Crossover Study ◽  
Healthy Volunteers ◽  
Maximum Concentration ◽  
Nutritional Supplement ◽  
Healthy Adults ◽  
Time Curve ◽  
Fasted State ◽  
Concentration Time ◽  
Randomized Crossover Study

ABSTRACT We conducted a randomized, crossover study in healthy adults to examine the effects of a nutritional supplement (Boost Plus) on posaconazole pharmacokinetics. In this study, coadministration of posaconazole with Boost Plus increased the maximum concentration of posaconazole in serum and area under the concentration-time curve from 0 to 72 h values 3.4- and 2.6-fold, respectively, compared to those for the fasted state.

Clinically Significant Pharmacokinetic Interaction between Colchicine and Ritonavir in Healthy Volunteers

2013 ◽  
Vol 5 ◽  
pp. CMT.S10561 ◽  
Author(s):  
Suman Wason ◽  
Jennifer L. DiGiacinto ◽  
Matthew W. Davis
Keyword(s):  
Healthy Volunteers ◽  
Multiple Dose ◽  
Plasma Concentrations ◽  
Pharmacokinetic Interaction ◽  
Concomitant Administration ◽  
Study Data ◽  
Open Label ◽  
Time Curve ◽  
Clinically Significant ◽  
Cyp3a4 Enzyme

Colchicine is a substrate for cytochrome 3A4 (CYP3A4) enzyme and P-glycoprotein efflux transporter (P-gp); consequently, concomitant administration with drugs that inhibit these have the potential to cause clinically significant increases in colchicine plasma concentrations and precipitate adverse events. Ritonavir, a protease inhibitor, elicits potent CYP3A4 and P-gp inhibitory activity. In this open-label, nonrandomized, one-sequence, two-period study, 24 healthy volunteers received a single 0.6-mg dose of colchicine alone and together with multiple-dose ritonavir (100 mg twice daily for 4 days) to evaluate drug-drug interactions. Serial blood samples were collected for the determination of colchicine plasma concentrations. Standard pharmacokinetic parameter values were calculated along with 90% confidence intervals (ie, area under the concentration-time curve plasma from time zero to the time of last quantifiable concentration [AUC0-t and AUC0-∞], maximum drug concentration [Cmax]) for colchicine alone and colchicine combined with multiple-dose ritonavir. The mean Cmax and AUC0-t were significantly increased (170% and 245%, respectively) when colchicine was coadministered with ritonavir as compared with colchicine alone. Study data confirm the need for a dose adjustment (approximately 50% reduction) when colchicine is coadministered with strong CYP3A/P-gp inhibitors.

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