scholarly journals Pharmacokinetics and Absorption of Posaconazole Oral Suspension under Various Gastric Conditions in Healthy Volunteers

2008 ◽  
Vol 53 (3) ◽  
pp. 958-966 ◽  
Author(s):  
Gopal Krishna ◽  
Allen Moton ◽  
Lei Ma ◽  
Matthew M. Medlock ◽  
James McLeod
Keyword(s):  
Proton Pump ◽  
Gastric Motility ◽  
Nutritional Supplement ◽  
Gastric Ph ◽  
High Fat ◽  
Time Curve ◽  
Concentration Time ◽  
Dosing Frequency ◽  
Randomized Crossover Study ◽  
Fat Meal

ABSTRACT A four-part, randomized, crossover study with healthy subjects evaluated the effects of gastric pH, the dosing frequency and prandial state, food consumption timing, and gastric motility on the absorption of posaconazole. In part 1, a single dose (SD) of posaconazole (400 mg) was administered alone or with an acidic beverage or a proton pump inhibitor (PPI), or both. In part 2, posaconazole (400 mg twice daily and 200 mg four times daily) was administered for 7 days with and without a nutritional supplement (Boost). In part 3, an SD of posaconazole (400 mg) was administered while the subjects were fasting and before, during, and after a high-fat meal. In part 4, an SD of posaconazole (400 mg) and the nutritional supplement were administered alone, with metoclopramide, and with loperamide. Compared to the results obtained with posaconazole alone, administration with an acidic beverage increased the posaconazole maximum concentration in plasma (C max) and the area under the concentration-time curve (AUC) by 92% and 70%, respectively, whereas a higher gastric pH decreased the posaconazole C max and AUC by 46% and 32%, respectively. Compared to the results obtained with posaconazole alone, posaconazole at 400 mg or at 200 mg plus the nutritional supplement increased the posaconazole C max and AUC by 65% and 66%, respectively, and by up to 137% and 161%, respectively. Administration before a high-fat meal increased the C max and the AUC by 96% and 111%, respectively, while administration during and after the meal increased the C max and the AUC by up to 339% and 387%, respectively. Increased gastric motility decreased the C max and the AUC by 21% and 19%, respectively. Strategies to maximize posaconazole exposure in patients with absorption difficulties include administration with or after a high-fat meal, with any meal or nutritional supplement, with an acidic beverage, or in divided doses and the avoidance of proton pump inhibitors.

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 Effects of a High-Fat Meal on the Relative Oral Bioavailability of Piperaquine

2005 ◽  
Vol 49 (6) ◽  
pp. 2407-2411 ◽  
Author(s):  
Ing-Kye Sim ◽  
Timothy M. E. Davis ◽  
Kenneth F. Ilett
Keyword(s):  
Oral Bioavailability ◽  
Geometric Mean ◽  
Pharmacokinetic Analysis ◽  
Lipid Solubility ◽  
Fasting State ◽  
High Fat ◽  
Time Curve ◽  
Hematological Indices ◽  
Concentration Time ◽  
Fat Meal

ABSTRACT Piperaquine (PQ) is an antimalarial drug whose high lipid solubility suggests that its absorption can be increased by a high-fat meal. We examined the pharmacokinetics of PQ phosphate (500 mg given orally) in the fasting state and after a high-fat meal in eight healthy Caucasian volunteers (randomized crossover). Plasma PQ concentration-time profiles were analyzed by using noncompartmental pharmacokinetic analysis. In the fed state, the geometric mean C max increased by 213%, from 21.0 to 65.8 μg/liter (P < 0.001). The time of C max was not significantly different between the fasting and fed states. The geometric mean area under the concentration-time curve from zero onward (AUC0-∞) increased by 98%, from 3,724 to 7,362 μg h/liter (P = 0.006). The oral bioavailability of PQ relative to the fasting state was 121% greater after the high-fat meal (95% confidence interval, 26 to 216% increase; P = 0.020). The side effects, postural blood pressure changes, electrocardiographic corrected QT interval, serum glucose, and other biochemical and hematological indices were similar in the fasting and fed states over 28 days of follow-up.

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.

scholarly journals Posaconazole Tablet Pharmacokinetics: Lack of Effect of Concomitant Medications Altering Gastric pH and Gastric Motility in Healthy Subjects

2014 ◽  
Vol 58 (7) ◽  
pp. 4020-4025 ◽  
Author(s):  
Walter K. Kraft ◽  
Peter S. Chang ◽  
Marlou L. P. S. van Iersel ◽  
Hetty Waskin ◽  
Gopal Krishna ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Gastric Motility ◽  
Maximum Concentration ◽  
Geometric Mean ◽  
Gastric Ph ◽  
Oral Suspension ◽  
Open Label ◽  
Time Curve ◽  
Concentration Time ◽  
Concomitant Medications

ABSTRACTPosaconazole oral suspension is an extended-spectrum triazole that should be taken with food to maximize absorption. A new posaconazole tablet formulation has demonstrated improved bioavailability over the oral suspension in healthy adults in a fasting state. This study evaluated the effects of concomitant medications altering gastric pH (antacid, ranitidine, and esomeprazole) and gastric motility (metoclopramide) on the pharmacokinetics of posaconazole tablets. This was a prospective open-label 5-way crossover study in 20 healthy volunteers. In each treatment period, a single 400-mg dose (4 100-mg tablets) of posaconazole was administered alone or with 20 ml antacid (2 g of aluminum hydroxide and 2 g of magnesium hydroxide), ranitidine (150 mg), esomeprazole (40 mg), or metoclopramide (15 mg). There was a ≥10-day washout between treatment periods. Posaconazole exposure, time to maximum concentration of drug in serum (Tmax), and apparent terminal half-life (t1/2) were similar when posaconazole was administered alone or with medications affecting gastric pH and gastric motility. Geometric mean ratios (90% confidence intervals [CIs]) of the area under the concentration-time curve from time zero to infinity (AUC0–inf) (posaconazole with medications affecting gastric pH and gastric motility versus posaconazole alone) were 1.03 (0.88–1.20) with antacid, 0.97 (0.84–1.12) with ranitidine, 1.01 (0.87–1.17) with esomeprazole, and 0.93 (0.79–1.09) with metoclopramide. Geometric mean ratios (90% CIs) of the maximum concentration of drug in serum (Cmax) were 1.06 (0.90–1.26) with antacid, 1.04 (0.88–1.23) with ranitidine, 1.05 (0.89–1.24) with esomeprazole, and 0.86 (0.73–1.02) with metoclopramide. In summary, in healthy volunteers, the pharmacokinetics of a single 400-mg dose of posaconazole tablets was not altered to a clinically meaningful extent when posaconazole was administered alone or with medications affecting gastric pH or gastric motility.

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.

scholarly journals Effects of food and sucralfate on a single oral dose of 500 milligrams of levofloxacin in healthy subjects.

1997 ◽  
Vol 41 (10) ◽  
pp. 2196-2200 ◽  
Author(s):  
L J Lee ◽  
B Hafkin ◽  
I D Lee ◽  
J Hoh ◽  
R Dix
Keyword(s):  
Oral Dose ◽  
Healthy Subjects ◽  
High Fat ◽  
Time Curve ◽  
Mean Values ◽  
Treatment Groups ◽  
The Mean ◽  
The Individual ◽  
Individual Profiles ◽  
Fat Meal

The effects of food and sucralfate on the pharmacokinetics of levofloxacin following the administration of a single 500-mg oral dose were investigated in a randomized, three-way crossover study with young healthy subjects (12 males and 12 females). Levofloxacin was administered under three conditions: fasting, fed (immediately after a standardized high-fat breakfast), and fasting with sucralfate given 2 h following the administration of levofloxacin. The concentrations of levofloxacin in plasma and urine were determined by high-pressure liquid chromatography. By noncompartmental methods, the maximum concentration of drug in serum (Cmax), the time to Cmax (Tmax), the area under the concentration-time curve (AUC), half-life (t1/2), clearance (CL/F), renal clearance (CLR), and cumulative amount of levofloxacin in urine (Ae) were estimated. The individual profiles of the drug concentration in plasma showed little difference among the three treatments. The only consistent effect of the coadministration of levofloxacin with a high-fat meal for most subjects was that levofloxacin absorption was delayed and Cmax was slightly reduced (Tmax, 1.0 and 2.0 h for fasting and fed conditions, respectively [P = 0.002]; Cmax, 5.9 +/- 1.3 and 5.1 +/- 0.9 microg/ml [90% confidence interval = 0.79 to 0.94] for fasting and fed conditions, respectively). Sucralfate, which was administered 2 h after the administration of levofloxacin, appeared to have no effect on levofloxacin's disposition compared with that under the fasting condition. Mean values of Cmax and AUC from time zero to infinity were 6.7 +/- 3.2 microg/ml and 47.9 +/- 8.4 microg x h/ml, respectively, following the administration of sucralfate compared to values of 5.9 +/- 1.3 microg/ml and 50.5 +/- 8.1 microg x h/ml, respectively, under fasting conditions. The mean t1/2, CL/F, CLR, and Ae values were similar among all three treatment groups. In conclusion, the absorption of levofloxacin was slightly delayed by food, although the overall bioavailability of levofloxacin following a high-fat meal was not altered. Finally, sucralfate did not alter the disposition of levofloxacin when sucralfate was given 2 h after the administration of the antibacterial agent, thus preventing a potential drug-drug interaction.

scholarly journals Effect of Antacids and Ranitidine on the Single-Dose Pharmacokinetics of Fosamprenavir

2005 ◽  
Vol 49 (1) ◽  
pp. 467-469 ◽  
Author(s):  
Susan L. Ford ◽  
Mary B. Wire ◽  
Yu Lou ◽  
Katherine L. Baker ◽  
Daniel S. Stein
Keyword(s):  
Single Dose ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Maximum Concentration ◽  
Receptor Antagonists ◽  
Time Curve ◽  
Concentration Time

ABSTRACT Single doses of MAALOX TC and ranitidine were administered separately with 1,400 mg of fosamprenavir (FPV). MAALOX TC decreased the area under the concentration-time curve from 0 to 24 h (AUC0-24) for plasma amprenavir (APV) by 18% and the maximum concentration of drug in serum (C max) by 35%; the plasma APV concentration at 12 h (C 12) increased by 14%. Ranitidine at 300 mg decreased the AUC0-24 for plasma APV by 30% and C max by 51%; C 12 was unchanged. FPV may be coadministered with antacids without concern and without separation in dosing; however, caution is recommended when FPV is coadministered with histamine2- receptor antagonists or proton pump inhibitors.

Comparative Bioavailability of a Microsize and Ultramicrosize Griseofulvin Formulation in Man

1982 ◽  
Vol 10 (4) ◽  
pp. 274-277 ◽  
Author(s):  
C Lin ◽  
J Lim ◽  
C DiGiore ◽  
R Gural ◽  
bS Symchowicz
Keyword(s):  
Plasma Concentration ◽  
Maximum Plasma Concentration ◽  
Maximum Plasma ◽  
Healthy Male ◽  
Time Curve ◽  
Concentration Time ◽  
Comparative Bioavailability ◽  
Plasma Concentration Time Curve ◽  
Randomized Crossover Study ◽  
Curve Maximum

The bioavailability of 500 mg of a microsize formulation of griseofulvin has been compared to two new ultramicrosize griseofulvin formulations, two 165 mg tablets and a 330 mg tablet, in sixteen healthy, male, volunteers in a randomized crossover study design. Based on the griseofulvin plasma levels measured at specified times over a 48-hour period, the major bioavailability parameters (i.e., area under plasma concentration-time curve, maximum plasma concentration, and time to reach maximum plasma concentration) were determined and statistically evaluated. The results showed that one 330 mg ultramicrosize tablet is bioequivalent to two 165 mg ultramicrosize griseofulvin tablets and that either ultramicrosize griseofulvin dosage regimen is bioequivalent to 500 mg of the microsize griseofulvin formulation.

scholarly journals Atogepant and sumatriptan: no clinically relevant drug–drug interactions in a randomized, open-label, crossover trial

2021 ◽  
Author(s):  
Ramesh Boinpally ◽  
Abhijeet Jakate ◽  
Matthew Butler ◽  
Antonia Periclou
Keyword(s):  
Plasma Concentration ◽  
Crossover Trial ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Geometric Mean ◽  
Open Label ◽  
Time Curve ◽  
Concentration Time ◽  
Pharmacokinetic Interactions ◽  
Randomized Crossover Study

Aim: To evaluate pharmacokinetic interactions of atogepant with sumatriptan, an open-label, randomized, crossover study was conducted. Patients & methods: Thirty healthy adults received atogepant 60 mg, sumatriptan 100 mg, or coadministered drugs. Primary end point was geometric mean ratios (GMRs) and 90% CIs of interventions for area under the plasma concentration–time curve from time 0 to t (AUC0-t) or infinity (AUC0-∞) and peak plasma concentration (Cmax). Results: Atogepant GMRs for AUC0-t and AUC0-∞ versus with sumatriptan were within 90% CI 0.80–1.25, indicating no interaction; atogepant Cmax was reduced by 22% (GMR: 0.78; 90% CI: 0.69–0.89) with sumatriptan. Sumatriptan GMRs for AUC0-t, AUC0-∞ and Cmax versus with atogepant were within 90% CI 0.80–1.25. Conclusion: Atogepant with sumatriptan had no clinically relevant pharmacokinetic interactions.

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