scholarly journals Lack of effect of vancomycin and gentamicin on auditory function in guinea pigs.

1996 ◽  
Vol 40 (5) ◽  
pp. 1098-1103
Author(s):  
K Nishihara ◽  
T Shimizu ◽  
H Kotaki ◽  
Y Sawada ◽  
T Okuno ◽  
...  
Keyword(s):  
Guinea Pigs ◽  
Hearing Threshold ◽  
Plasma Drug Concentration ◽  
Pharmacokinetic Parameters ◽  
Plasma Drug ◽  
Auditory Function ◽  
Time Data ◽  
Concentration Time ◽  
Penetration Ratio ◽  
Combined Administration

The dispositions of vancomycin (VCM) and gentamicin (GM) in plasma and perilymph after single and multiple administrations and the effects of multiple administrations of VCM or GM alone and the combination of both drugs on auditory function were studied in male guinea pigs. The pharmacokinetic parameters of VCM and GM obtained from plasma drug concentration-time data after single and multiple (22 days) intramuscular administrations of VCM (200 mg/kg of body weight) alone and GM (50 mg/kg) alone were not significantly different from those after combined administration of VCM (200 mg/kg) and GM (50 mg/kg). There was no change in the penetration ratio of VCM and GM into perilymph between administration of VCM or GM alone and the combination of both drugs. Furthermore, the hearing threshold of guinea pigs was not affected by VCM or GM alone or the combination of both drugs within the range of therapeutic VCM and GM levels in plasma in humans.

scholarly journals PHARMACOKINETIC COMPARISON OF MONTELUKAST SODIUM FORMULATIONS AFTER A SINGLE ORAL DOSE IN HEALTHY GUINEA PIGS

2019 ◽  
pp. 165-169
Author(s):  
NEELAM SINGH ◽  
Giriraj T Kulkarni ◽  
Yatendra Kumar ◽  
GIRIRAJ T KULKARNI
Keyword(s):  
Plasma Concentration ◽  
Oral Dose ◽  
Single Oral Dose ◽  
Guinea Pigs ◽  
Elimination Rate ◽  
Pharmacokinetic Parameters ◽  
Time Data ◽  
Concentration Time ◽  
Montelukast Sodium ◽  
Significant Difference

Objective: Pharmacokinetic evaluation of montelukast sodium chronomodulated capsules (sustained-release solid dispersion of drug enclosed in pH-sensitive film-coated hard gelatin shell) and marketed tablets has been carried out in this study. Methods: A single oral dose of prepared capsules and marketed conventional tablets was administered in healthy male Dunkin-Hartley albino guinea pigs. Blood samples were collected at different time intervals and plasma concentration of drug was determined by reversed-phase high-performance liquid chromatography. Different pharmacokinetic parameters were assessed from plasma drug concentration-time profile by one-compartment model, first-order kinetics. Results: Pharmacokinetic parameters such as time to reach maximum concentration, elimination rate constant, elimination half-life, and mean residence time data indicates that drug release from chronomodulated capsules is significantly prolonged with initial release lag time of 3.5–4 h in comparison with marketed conventional tablets. However, maximum drug plasma concentration, area under the concentration-time curve, and apparent volume of distribution values show non-significant difference between capsules and marketed tablets. Conclusion: The findings specified that capsules were providing time controlled delivery of drug at a desired rate for prolonged time, which may be helpful for the prevention of episodic attack of asthma in early morning hours.

scholarly journals Complexation of Z-ligustilide with hydroxypropyl-β-cyclodextrin to improve stability and oral bioavailability

2014 ◽  
Vol 64 (2) ◽  
pp. 211-222 ◽  
Author(s):  
Yapeng Lu ◽  
Siyuan Liu ◽  
Yu Zhao ◽  
Li Zhu ◽  
Shuqin Yu
Keyword(s):  
Inclusion Complex ◽  
Oral Bioavailability ◽  
Compartment Model ◽  
Plasma Drug Concentration ◽  
Absolute Bioavailability ◽  
Plasma Drug ◽  
Concentration Time ◽  
Kneading Method ◽  
Vis Spectroscopy ◽  
The Stability

Abstract To improve the stability and oral bioavailability of Z-ligustilide (LIG), the inclusion complex of LIG with hydroxypropyl- β-cyclodextrin (HP-β-CD) was prepared by the kneading method and characterized by UV-Vis spectroscopy, differential thermal analysis (DTA) and Fourier transform infrared (FTIR) spectroscopy. LIG is capable of forming an inclusion complex with HP-b-CD and the stoichiometry of the complex was 1:1. Stability of the inclusion complex against temperature and light was greatly enhanced compared to that of free LIG. Further, oral bioavailability of LIG and the inclusion complex in rats were studied and the plasma drug concentration-time curves fitted well with the non-compartment model to estimate the absolute bioavailability, which was 7.5 and 35.9 %, respectively. In conclusion, these results show that LIG/HP-β-CD complexation can be of great use for increasing the stability and biological efficacy of LIG

Prediction of Plasma Drug Concentration Profiles and Pharmacokinetic Parameters of Nifedipine Commercial Tablets using the Convolution Method

2021 ◽  
pp. 5380-5384
Author(s):  
Hamzah Maswadeh ◽  
Ahmed A. H. Abdellatif ◽  
A. Amin Mohammed ◽  
Aiman Y. Alwadi ◽  
A. Ibrahim Mohamed
Keyword(s):  
Drug Concentration ◽  
Elimination Rate ◽  
Volume Of Distribution ◽  
Plasma Drug Concentration ◽  
Pharmacokinetic Parameters ◽  
Concentration Profiles ◽  
Plasma Drug ◽  
First Order ◽  
Convolution Method

The aim of this study was to predict the blood/plasma drug concentration profiles for five brand of nifedipine present on the Saudi Arabia market by using the numerical convolution method and to estimate the pharmacokinetic parameters (Cmax, Tmax, Ka, K and Vd) by the application of the residual method to the predicted plasma drug concentration profiles. Results showed that the higher Cmax was 118.95ng/ml for brand A2 and the lower Cmax was 72.29ng/ml for brand A3. The Tmax was ranged from 2.3 hr to 4.9 hr for brands A2 and A3 respectively. The total area under plasma drug concentration curve (AUCinf.) was in lower value equal to 585.59 ng x hr/ml for brand A2 and the higher value was for brand A5 equal to 743.52ng x hr/ml. The volume of distribution was also increased from 52.5 L for free nifidipine to 72 L for brand A1. The predicted first order elimination rate constant was decreased from 0.34 hr-1 for free nifedipine to 0.17 hr-1 for brand A3. The half-life of nifedapine was increased from 2 hours for free drug to 3.93 hours for brand A3. From this study it can be concluded that brands present in the market that shows similarity in accordance to the Dissimilarity factor f1 are not always guaranty that they will be bioequivalent in vivo and vice versa. Also, this study indicates that the method of convolution is a useful tool for prediction of bioequivalence of different brands present on the market.

scholarly journals ALTERATION OF PHARMACOKINETIC PARAMETERS OF PENTOXIFYLLINE USING NATURAL MUCOADHESIVE POLYMERS

2019 ◽  
pp. 153-157
Author(s):  
GNANASEKARAN JOHN SELVARAJ ◽  
ARUL BALASUBRAMANIAN ◽  
KOTHAI RAMALINGAM
Keyword(s):  
Drug Concentration ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Fold Increase ◽  
Ocimum Basilicum ◽  
Plasma Drug Concentration ◽  
Pharmacokinetic Parameters ◽  
Plasma Drug ◽  
Time Curve ◽  
Significant Difference

Objective: The present study was aimed to alter the pharmacokinetic parameters of the drug pentoxifylline using a novel natural mucoadhesive polymer from two different plants, Manilkara zapotta Linn and Ocimum basilicum Linn. Methods: The polymer was isolated and six batches of mucoadhesive tablets of pentoxifylline was formulated with 3 different concentrations of each polymer. The best formulation from each of the polymer was selected and administered to rabbits and the plasma drug concentration was compared with the marketed formulation. The pharmacokinetic parameters such as such as Cmax, tmax, AUC, AUMC, λz, t1/2, and MRT were determined. Results: The plasma drug concentration vs time curve shows the extended-release of pentoxifylline when compared with the conventional marketed formulation. The results show that there is no change in the peak plasma concentration, but the significant difference was observed in t½, which showed approximately 2.5 fold increase from 2.44 to 6.87 h and the AUC showed five-fold increase from 22.40 to 117.19 μg*h/ml, and other pharmacokinetic parameters, when compared with the marketed formulation. Conclusion: The isolated polymer from the plants Manilkara zapotta Linn. and Ocimum basilicum Linn can be used as a carrier for developing mucoadhesive formulations and it alter the pharmacokinetic of pentoxifylline positively.

scholarly journals Pharmacokinetics of Florfenicol in Healthy Pigs and in Pigs Experimentally Infected with Actinobacillus pleuropneumoniae

2003 ◽  
Vol 47 (2) ◽  
pp. 820-823 ◽  
Author(s):  
Jianzhong Liu ◽  
Ki-Fai Fung ◽  
Zhangliu Chen ◽  
Zhenling Zeng ◽  
Jie Zhang
Keyword(s):  
Half Life ◽  
Clinical Signs ◽  
Actinobacillus Pleuropneumoniae ◽  
Pharmacokinetic Parameters ◽  
X Rays ◽  
Time Data ◽  
Time Curve ◽  
Chromatography Method ◽  
Concentration Time ◽  
Significant Difference

ABSTRACT A comparative in vivo pharmacokinetic study of florfenicol was conducted in 18 crossbred pigs infected with Actinobacillus pleuropneumoniae following intravenous (i.v.), intramuscular (i.m.), or oral (p.o.) administration of a single dose of 20 mg/kg. The disease model was confirmed by clinical signs, X rays, pathohistologic examinations, and organism isolation. Florfenicol concentrations in plasma were determined by a validated high-performance liquid chromatography method with UV detection at a wavelength of 223 nm. Pharmacokinetic parameters were calculated by using the MCPKP software (Research Institute of Traditional Chinese Veterinary Medicine, Lanzhou, China). The disposition of florfenicol after a single i.v. bolus was described by a two-compartment model with values for the half-life at α phase (t 1/2α), the half-life at β phase (t 1/2β), the area under the concentration-time curve (AUC0-∞), and the volume of distribution at steady state (V ss) of 0.37 h, 2.91 h, 64.86 μg · h/ml, and 1.2 liter/kg, respectively. The concentration-time data fitted the one-compartment (after i.m.) and two-compartment (after p.o.) models with first-order absorption. The values for the maximum concentration of drug in serum (C max), t 1/2α, t 1/2β, and bioavailability after i.m. and p.o. dosing were 4.00 and 8.11 μg/ml, 0.12 and 3.91 h, 13.88 and 16.53 h, and 122.7 and 112.9%, respectively, for the two models. The study showed that florfenicol was absorbed quickly and completely, distributed widely, and eliminated slowly in the infected pigs, and there was no statistically significant difference between the pharmacokinetic profiles for the infected and healthy pigs.

scholarly journals ALTERATION OF PHARMACOKINETIC PARAMETERS OF PROTON PUMP INHIBITORS USING TRANSDERMAL DRUG DELIVERY SYSTEM

2021 ◽  
pp. 371-375
Author(s):  
M. R. SHIVALINGAM ◽  
ARUL BALASUBRAMANIAN ◽  
KOTHAI RAMALINGAM
Keyword(s):  
Plasma Concentration ◽  
Residence Time ◽  
Proton Pump ◽  
Drug Concentration ◽  
Mean Residence Time ◽  
Fold Increase ◽  
Plasma Drug Concentration ◽  
Pharmacokinetic Parameters ◽  
Plasma Drug ◽  
Transdermal Patches

Objective: The present study was aimed to find out the effect of transdermal patches of proton pump inhibitors pantoprazole and esomeprazole on the alteration of pharmacokinetic parameters of these drugs. Methods: The transdermal patches were formulated by the solvent evaporation technique using polymers HPMC E5 with PVP K 30 and HPMC E5 with Eudragit L100 in different ratios. The best formulation from each of the drug pantoprazole and esomeprazole was selected and administered to rabbits and the plasma drug concentration was compared with the marketed formulation. The pharmacokinetic parameters such as maximum plasma concentration (Cmax), time to reach Cmax (tmax), area under the curve (AUC), area under first moment curve (AUMC), elimination rate constant (λz), biological half-life (t1/2), and mean residence time (MRT) were determined. Results: The plasma drug concentration vs time curve shows the extended-release of the drugs pantoprazole and esomeprazole when compared with the marketed formulation. The results show that there is no change in the peak plasma concentration, but a significant difference was observed in all the pharmacokinetic parameters. The AUC showed 6 fold increase for pantoprazole from 8.91 to 55.20 μg*h/ml and 3.5 fold increase for the drug esomeprazole from 7.86 to 28.53 μg*h/ml, and the mean residence time also showed 2 fold increase for the transdermal patches when compared with the marketed formulations. Conclusion: The increase in tmax, AUC, and MRT values of the formulated transdermal patches with the values of the marketed formulation of both the drugs, revealed that the transdermal patches can be used to deliver the drug for an extended period and also can alter the pharmacokinetics of pantoprazole and esomeprazole.

Drug Degradation during HPLC Analysis of Aztreonam: Effect on Pharmacokinetic Parameter Estimation

1994 ◽  
Vol 28 (4) ◽  
pp. 444-446
Author(s):  
Lawrence V. Friedrich ◽  
Roger L. White ◽  
Michael B. Kays ◽  
David S. Burgess
Keyword(s):  
Serum Concentration ◽  
Pharmacokinetic Parameter ◽  
Hplc Analysis ◽  
Statistical Significance ◽  
Pharmacokinetic Parameters ◽  
Parameter Estimates ◽  
Time Data ◽  
Drug Degradation ◽  
Concentration Time ◽  
The Impact

OBJECTIVE: To assess the impact of degradation of aztreonam, a beta-lactam antibiotic, during HPLC analysis on pharmacokinetic parameter estimates. METHODS: The baseline (B) serum concentration-time data from a published pharmacokinetic study of aztreonam were degraded using first-order equations and a degradation rate constant (0.014 h-1) determined from a preliminary degradation study. Samples were mathematically degraded for autosampler run times of 8–13 h (D1) to approximate a normal work day and for autosampler run times of 16–17 h (D2) and compared with B data. It was assumed that B data were nondegraded and that changes in chromatography were the result of degradation of azetreonam and not to any changes in chromatographic conditions. A two-compartment model was used to fit the data and pharmacokinetic parameters were calculated using standard equations. Statistical significance between all pharmacokinetic parameters for B and D1 and B and D2 was determined using the paired, two-tailed Student's t-test. RESULTS: Increased variability was noted for all pharmacokinetic parameters for D1 and D2 compared with B. Statistically significant differences were found for clearance (B <D1, p=0.0095 and B <D2, p=0.0194), steady-state volume of distribution (B <D2, p=0.0392), and area under the serum concentration-time curve (B >D1, p=0.0497). CONCLUSIONS: Aztreonam degradation resulted in increased variability in pharmacokinetic parameter estimates. Investigators should be cognizant of this and preliminary studies should be performed to characterize degradation for the length of the expected autosampler run.

scholarly journals The Influence of the Different Disposition Characteristics of Snake Toxins on the Pharmacokinetics of Snake Venom

Toxins ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 188 ◽  
Author(s):  
Suchaya Sanhajariya ◽  
Geoffrey K. Isbister ◽  
Stephen B. Duffull
Keyword(s):  
Molecular Weight ◽  
Snake Venom ◽  
Time Course ◽  
Total Concentration ◽  
Weight Fraction ◽  
Pharmacokinetic Parameters ◽  
Time Data ◽  
Molecular Weights ◽  
Concentration Time ◽  
Wide Range

Snake venom is comprised of a combination of different proteins and peptides with a wide range of molecular weights and different disposition processes inherent to each compound. This causes venom to have a complex exposure profile. Our study investigates 1) how each molecular weight fraction (toxin) of venom contributes to the overall time course of the snake venom, and 2) the ability to determine toxin profiles based on the profile of the overall venom only. We undertook an in silico simulation and modelling study. Sixteen variations of venom, comprising of two to nine toxins with different molecular weights were investigated. The pharmacokinetic parameters (i.e., clearance,  C L , and volume of distribution,  V ) of each toxin were generated based on a log-linear relationship with molecular weight. The concentration–time data of each toxin were simulated for 100 virtual patients using MATLAB and the total concentration–time data of each toxin were modelled using NONMEM. We found that the data of sixteen mixtures were best described by either two- or three-compartment models, despite the venom being made up of more than three different toxins. This suggests that it is generally not possible to determine individual toxin profiles based on measurements of total venom concentrations only.

scholarly journals Effect of Food on the Bioavailability of Stavudine in Subjects with Human Immunodeficiency Virus Infection

1998 ◽  
Vol 42 (9) ◽  
pp. 2295-2298 ◽  
Author(s):  
Sanjeev Kaul ◽  
Barbara Christofalo ◽  
Ralph H. Raymond ◽  
Michael B. Stewart ◽  
Catherine M. Macleod
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hiv Infection ◽  
Drug Concentration ◽  
Plasma Drug Concentration ◽  
Maximum Plasma ◽  
Fasting State ◽  
Plasma Drug ◽  
Cell Counts ◽  
Concentration Time ◽  
Immunodeficiency Virus

ABSTRACT A randomized, three-way crossover study was carried out to determine the effects of food ingestion on the pharmacokinetics of stavudine (d4T). Fifteen subjects with human immunodeficiency virus (HIV) infection and CD4+ cell counts of ≥200/μl received 70 mg of d4T in a fasting state or 1 h before or 5 min after a standardized high-fat breakfast. A 7- to 15-day washout period was included between treatments. Blood and urine were collected before and for 10 h after dosing, and plasma and urine d4T concentrations were determined with a validated radioimmunoassay. Plasma drug concentration-time data were analyzed with a noncompartmental model. The mean maximum plasma drug concentration (C max) and the time toC max (T max) for administration of d4T after a meal were significantly lower and longer (P = 0.0001 for both measures) than those observed in the fasting state, although the area under the concentration-time curve from time zero to infinity (AUC0–∞) was not significantly different. Neither of these parameters was significantly altered when d4T was taken 1 h before a meal. The bioavailability of d4T taken after a meal was 95% of that observed in the fasting state, and it was 97% when d4T was administered before a meal (P > 0.05 for both comparisons with the fasting state). The results of this study indicate that (i) ingestion of food does not affect the bioavailability of d4T and that patients with HIV infection can take it without regard to meals, and (ii) absorption is essentially complete within 1 h when d4T is administered in the fasted state.

scholarly journals Single-Dose Pharmacokinetics of a Pleconaril (VP63843) Oral Solution in Children and Adolescents

1999 ◽  
Vol 43 (3) ◽  
pp. 634-638 ◽  
Author(s):  
Gregory L. Kearns ◽  
Susan M. Abdel-Rahman ◽  
Laura P. James ◽  
Douglas L. Blowey ◽  
James D. Marshall ◽  
...  
Keyword(s):  
Single Dose ◽  
Oral Dose ◽  
Rate Constant ◽  
Pediatric Patients ◽  
Elimination Rate ◽  
Pharmacokinetic Parameters ◽  
Parameter Estimates ◽  
Time Data ◽  
Concentration Time ◽  
The Mean

ABSTRACT Pleconaril is an orally active, broad-spectrum antipicornaviral agent which demonstrates excellent penetration into the central nervous system, liver, and nasal epithelium. In view of the potential pediatric use of pleconaril, we conducted a single-dose, open-label study to characterize the pharmacokinetics of this antiviral agent in pediatric patients. Following an 8- to 10-h period of fasting, 18 children ranging in age from 2 to 12 years (7.5 ± 3.1 years) received a single 5-mg/kg of body weight oral dose of pleconaril solution administered with a breakfast of age-appropriate composition. Repeated blood samples (n = 10) were obtained over 24 h postdose, and pleconaril was quantified from plasma by gas chromatography. Plasma drug concentration-time data for each subject were fitted to the curve by using a nonlinear, weighted (weight = 1/Y calc) least-squares algorithm, and model-dependent pharmacokinetic parameters were determined from the polyexponential parameter estimates. Pleconaril was well tolerated by all subjects. A one-compartment open-model with first-order absorption best described the plasma pleconaril concentration-time profile in 13 of the subjects over a 24-h postdose period. Pleconaril pharmacokinetic parameters (means ± standard deviations) for these 13 patients were as follows. The maximum concentration of the drug in serum (C max) was 1,272.5 ± 622.1 ng/ml. The time to C max was 4.1 ± 1.5 h, and the lag time was 0.75 ± 0.56 h. The apparent absorption rate constant was 0.75 ± 0.48 1/h, and the elimination rate constant was 0.16 ± 0.07 1/h. The area under the concentration-time curve from 0 to 24 h was 8,131.15 ± 3,411.82 ng · h/ml. The apparent total plasma clearance was 0.81 ± 0.86 liters/h/kg, and the apparent steady-state volume of distribution was 4.68 ± 2.02 liters/kg. The mean elimination half-life of pleconaril was 5.7 h. The mean plasma pleconaril concentrations at both 12 h (250.4 ± 148.2 ng/ml) and 24 h (137.9 ± 92.2 ng/ml) after the single 5-mg/kg oral dose in children were higher than that from in vitro studies reported to inhibit >90% of nonpolio enterovirus serotypes (i.e., 70 ng/ml). Thus, our data support the evaluation of a 5-mg/kg twice-daily oral dose of pleconaril for therapeutic trials in pediatric patients with enteroviral infections.

Sign in / Sign up

Export Citation Format

Share Document