scholarly journals Effect of Calcium Carbonate on Bioavailability of Orally Administered Gemifloxacin

2003 ◽  
Vol 47 (7) ◽  
pp. 2158-2160 ◽  
Author(s):  
M. W. Pletz ◽  
P. Petzold ◽  
A. Allen ◽  
O. Burkhardt ◽  
H. Lode
Keyword(s):  
Calcium Carbonate ◽  
Oral Bioavailability ◽  
Half Life ◽  
Maximum Concentration ◽  
Time Curve ◽  
Concentration Time

ABSTRACT We investigated the effect of calcium carbonate on the oral bioavailability of gemifloxacin. Gemifloxacin was administered alone, 2 h before, simultaneously, or 2 h after calcium carbonate in 16 volunteers. Data for 320 mg of gemifloxacin alone were as follows: maximum concentration of drug in serum (C max),13 μg/ml; half-life, 7.33 h; and area under the concentration-time curve from 0 h to infinity (AUC∞), 6.79 μg · h/ml. Only simultaneous coadministration of calcium carbonate reduced C max (−17%) and AUC∞ (−21%) significantly.

Diet-induced modulation of pharmacokinetics of albendazole in Sahiwal cattle

2015 ◽  
Vol 90 (5) ◽  
pp. 555-560 ◽  
Author(s):  
P.K. Sanyal ◽  
D. Rawte ◽  
A.E. Kerketta ◽  
N.K. Kumbhakar ◽  
D. Kumar ◽  
...  
Keyword(s):  
Half Life ◽  
Maximum Concentration ◽  
Active Metabolite ◽  
Time Curve ◽  
Active Moiety ◽  
Concentration Time ◽  
Elimination Half ◽  
Green Fodder ◽  
Pre Treatment ◽  
Diet Type

AbstractThe influence of diet type and pre-treatment fasting on the kinetic disposition of albendazole was evaluated in Sahiwal heifers following oral and intra-ruminal administration of the drug. The anthelmintically active moiety albendazole sulphoxide appeared early and was eliminated early in cattle offered green fodder, with decreased maximum concentration (Cmax) and area under concentration–time curve (AUC) when the drug was administered both through oral and intra-ruminal routes. Further, the elimination half-life (t½β) revealed significantly increased values for albendazole sulphoxide in cattle administered albendazole through the intra-ruminal route. An increased AUC and t½β is reflective of increased bioavailability of albendazole in animals offered dry fodder. Increased values (P <  0.05) of Cmax, time to Cmax (Tmax), AUC and t½β for albendazole sulphoxide occurred in cattle with a pre-treatment 24-h fast, resulting in its increased bioavailability. Extrapolation of data of the active metabolite albendazole sulphoxide levels in terms of drug–parasite contact revealed increased exposure of parasites to the drug in cattle administered albendazole through the intra-ruminal route and with 24-h pre-treatment fasting.

scholarly journals Interaction between Grapefruit Juice and Praziquantel in Humans

2002 ◽  
Vol 46 (5) ◽  
pp. 1614-1616 ◽  
Author(s):  
Nelly Castro ◽  
Helgi Jung ◽  
Roberto Medina ◽  
Dinora González-Esquivel ◽  
Mario Lopez ◽  
...  
Keyword(s):  
Water Treatment ◽  
Oral Dose ◽  
Single Oral Dose ◽  
Half Life ◽  
Maximum Concentration ◽  
Grapefruit Juice ◽  
Time Curve ◽  
Elimination Half Life ◽  
Concentration Time ◽  
Elimination Half

ABSTRACT After a single oral dose of praziquantel with 250 ml of grapefruit juice, the area under the concentration-time curve and the maximum concentration in plasma of praziquantel (C max) were significantly increased (C max for water treatment, 637.71 ± 128.5 ng/ml; and C max for grapefruit juice treatment, 1,037.65 ± 305.7 ng/ml, P < 0.05). No statistically significant differences were found in the time to maximum concentration of drug in plasma or elimination half-life.

Efficacy of pharmacokinetic interactions between piperonyl butoxide and albendazole against gastrointestinal nematodiasis in goats

2015 ◽  
Vol 90 (5) ◽  
pp. 624-629 ◽  
Author(s):  
N.K. Kumbhakar ◽  
P.K. Sanyal ◽  
D. Rawte ◽  
D. Kumar ◽  
A.E. Kerketta ◽  
...  
Keyword(s):  
Body Weight ◽  
Half Life ◽  
Maximum Concentration ◽  
Piperonyl Butoxide ◽  
Time Curve ◽  
Concentration Time ◽  
Elimination Half ◽  
Concentration Maximum ◽  
Faecal Egg Count ◽  
Minimum Residence Time

AbstractTo test the hypothesis that modulation of hepatic microsomal sulphoxidation and sulphonation by the cytochrome P450 inhibitor piperonyl butoxide could increase bioavailability of albendazole, the present study was undertaken to understand the pharmacokinetics of albendazole in goats at a dose of 7.5 mg kg− 1 body weight with and without co-administration with piperonyl butoxide at 63.0 mg kg− 1 body weight. Plasma albendazole sulphoxide metabolite, the anthelmintically active moiety, reached its maximum concentration of 0.322 ± 0.045 μg ml− 1 and 0.384 ± 0.013 μg ml− 1 at 18 h and 24 h after administration of albendazole alone and co-administration of albendazole with piperonyl butoxide, respectively. Analysis of the data revealed statistically increased albendazole sulphoxide levels at 24 (P <  0.001), 30 (P <  0.001) and 36 h (P <  0.01) after administration of albendazole with piperonyl butoxide, with statistically increased levels of albendazole sulphone at 24, 30 and 48 h after administration. No significance difference (P > 0.05) in values of maximum concentration (normal and calculated) could be observed between groups of goats. However, values of time to reach the concentration maximum (normal and calculated), area under the concentration–time curve (0–∞ and calculated), minimum residence time, distribution half-life, elimination half-life and total area under the first movement of plasma drug concentration–time curve were significantly higher (P <  0.05) in plasma levels of albendazole sulphoxide in goats following single oral co-administration of albendazole with piperonyl butoxide. The faecal egg count reduction and lower 95% confidence limit for the group treated with albendazole alone were 97 and 68%, while for co-administration of albendazole and piperonyl butoxide the values were 99 and 97%, respectively. The ED50 for egg hatch was 0.196, indicating suspected resistance to benzimidazole anthelmintics. The drug combination proved efficacious against an albendazole-resistant nematode parasite population in goats.

scholarly journals ABT-773: Pharmacokinetics and Interactions with Ranitidine and Sucralfate

2003 ◽  
Vol 47 (3) ◽  
pp. 1129-1131 ◽  
Author(s):  
M. W. Pletz ◽  
V. Preechachatchaval ◽  
J. Bulitta ◽  
M. Allewelt ◽  
O. Burkhardt ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Half Life ◽  
Maximum Concentration ◽  
Time Curve ◽  
Concentration Time ◽  
Plasma Concentration Time Curve

ABSTRACT We assessed the pharmacokinetics and interaction of ABT-773 in 12 volunteers receiving ABT-773 alone or concomitantly with ranitidine or sucralfate. Data for 150 mg of ABT-773 were as follows: the maximum concentration of the drug in plasma (C max) was 318 ng/ml, its half-life was 5.66 h, and its area under the plasma concentration-time curve from 0 h to ∞ (AUC0-∞) was 1,662 ng · h/ml. Coadministration of ranitidine, reduced the C max (−25.7%) and AUC0-∞ (−15.8%) significantly. Sucralfate had no impact on the bioavailability of ABT-773.

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 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 Safety, toleration, and pharmacokinetics of intravenous azithromycin.

1996 ◽  
Vol 40 (11) ◽  
pp. 2577-2581 ◽  
Author(s):  
D R Luke ◽  
G Foulds ◽  
S F Cohen ◽  
B Levy
Keyword(s):  
Half Life ◽  
Active Drug ◽  
Slow Release ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Time Curve ◽  
Concentration Time ◽  
Elimination Half ◽  
The Mean ◽  
Male Subjects

To date, the clinical pharmacology of large intravenous doses of azithromycin has not been described. In the present study, single 2-h intravenous infusions of 1, 2, and 4 g of azithromycin were administered to three parallel groups (in each group, six received active drug and two received placebo) of healthy male subjects. Toleration (assessed by scores of subject-administered visual analog scale tests spanning 0 [good] to 10 [poor]), safety, pharmacokinetics, and serum motilin levels were monitored for up to 240 h after the start of each intravenous infusion. Mean nausea scores of 0.0, 0.0, 1.0, and 0.5 and abdominal cramping scores of 0.0, 0.0, 0.4, and 0.4 for 12-h periods after doses of 0, 1, 2, and 4 g of azithromycin, respectively, suggested that azithromycin was well tolerated. Because of the standardized 1-mg/ml infusates, all subjects in the 4-g dosing group complained of an urgent need to urinate. There were no consistent trends in endogenous motilin levels throughout the study. The maximum concentration of azithromycin in serum (10 micrograms/ml after a 4-g dose) and the area under the concentration-time curve (82 micrograms.h/ml after a 4-g dose) were dose related. The mean pharmacokinetic parameters were an elimination half-life of 69 h, total systemic clearance of 10 ml/min/kg, and a volume of distribution at steady state of 33.3 liters/kg. The pharmacokinetic results suggest that the long half-life of azithromycin is due to extensive uptake and slow release of the drug from tissues rather than an inability to clear the drug. Single intravenous doses of up to 4 g of azithromycin in healthy subjects are generally well tolerated, and quantifiable concentrations may persist in serum for 10 days or more.

scholarly journals Once-Daily Dosing in Dogs Optimizes Daptomycin Safety

2000 ◽  
Vol 44 (11) ◽  
pp. 2948-2953 ◽  
Author(s):  
F. B. Oleson ◽  
C. L. Berman ◽  
J. B. Kirkpatrick ◽  
K. S. Regan ◽  
J.-J. Lai ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Maximum Concentration ◽  
Time Curve ◽  
Once Daily ◽  
Gram Positive Bacteria ◽  
Concentration Time ◽  
Serum Creatine Phosphokinase ◽  
Lower Maximum ◽  
Resistant Strains ◽  
Lipopeptide Antibiotic

ABSTRACT Daptomycin is a novel lipopeptide antibiotic with potent bactericidal activity against most clinically important gram-positive bacteria, including resistant strains. Daptomycin has been shown to have an effect on skeletal muscle. To guide the clinical dosing regimen with the potential for the least effect on skeletal muscle, two studies were conducted with dogs to compare the effects of repeated intravenous administration every 24 h versus every 8 h for 20 days. The data suggest that skeletal-muscle effects were more closely related to the dosing interval than to either the maximum concentration of the drug in plasma or the area under the concentration-time curve. Both increases in serum creatine phosphokinase activity and the incidence of myopathy observed at 25 mg/kg of body weight every 8 h were greater than those observed at 75 mg/kg every 24 h despite the lower maximum concentration of drug in plasma. Similarly, the effects observed at 25 mg/kg every 8 h were greater than those observed at 75 mg/kg every 24 h at approximately the same area under the concentration-time curve from 0 to 24 h. Once-daily administration appeared to minimize the potential for daptomycin-related skeletal-muscle effects, possibly by allowing for more time between doses for repair of subclinical effects. Thus, these studies with dogs suggest that once-daily dosing of daptomycin in humans should have the potential to minimize skeletal-muscle effects. In fact, interim results of ongoing clinical trials, which have focused on once-daily dosing, appear to be consistent with this conclusion.

scholarly journals Preclinical Development of Inhalable D-Cycloserine and Ethionamide To Overcome Pharmacokinetic Interaction and Enhance Efficacy against Mycobacterium tuberculosis

2019 ◽  
Vol 63 (6) ◽  
Author(s):  
Rajeev Ranjan ◽  
Ashish Srivastava ◽  
Reena Bharti ◽  
Trisha Roy ◽  
Sonia Verma ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Bactericidal Activity ◽  
Half Life ◽  
Pharmacokinetic Interaction ◽  
Preclinical Development ◽  
Time Curve ◽  
Content Type ◽  
Concentration Time ◽  
Oral Doses ◽  
Plasma Half Life

ABSTRACT We compared the pharmacokinetics and efficacy of a combination of d-cycloserine (DCS) and ethionamide (ETO) via oral and inhalation routes in mice. The plasma half-life (t1/2) of oral ETO at a human-equivalent dose decreased from 4.63 ± 0.61 h to 1.64 ± 0.40 h when DCS was coadministered. The area under the concentration-time curve from 0 h to time t (AUC0–t) was reduced to one-third. Inhalation overcame the interaction. Inhalation, but not oral doses, reduced the lung CFU/g of Mycobacterium tuberculosis H37Rv from 6 to 3 log10 in 4 weeks, indicating bactericidal activity.

Sign in / Sign up

Export Citation Format

Share Document