Pharmacokinetics Of Amoxicillin Research Articles

Influence of Intramuscular Injection Sites on Pharmacokinetics of Amoxicillin in Olive Flounder (Paralichthys olivaceus) and Its Implication for Antibacterial Efficacy.

This study aimed to investigate the effects of different injection sites, including dorsal, cheek, and pectoral fin muscles, on the pharmacological properties of amoxicillin (AMOX) in olive flounder (Paralichthys olivaceus) after a single intramuscular (IM) injection of 40 mg/kg. The AMOX concentration was measured using high-performance liquid chromatography-tandem mass spectrometry, followed by a non-compartmental model analysis. The peak serum concentrations (Cmax) achieved 3 h after dorsal, cheek, and pectoral fin IM injections were 202.79, 203.96, and 229.59 μg/mL, respectively. The area under the concentration-time curve (AUC) was 1697.23, 2006.71, and 1846.61 µg/mL·h, respectively. The terminal half-life (t1/2λZ) was prolonged for cheek and pectoral fin IM injections (10.12 and 10.33 h, respectively) compared to dorsal IM injection (8.89 h). In the pharmacokinetic-pharmacodynamic analysis, a higher T > minimum inhibitory concentration (MIC) and AUC/MIC values were observed after AMOX was injected into the cheek and pectoral fin muscles compared to the dorsal muscle. Muscle residue depletion was below the maximum residue level from day 7 after IM injection at all three sites. These findings suggest that the cheek and pectoral fin sites provide advantages regarding systemic drug exposure and prolonged action compared with the dorsal site.

Evaluation of pharmacokinetic interactions of amoxicillin with ranitidine in healthy human volunteers of Karachi, Pakistan.

Polypharmacy may be considered as the customary practice to provide optimum care services to patients but inter resulted in augmented probability of multiple drug interaction. Keeping in view the importance of drug interaction possibility, this study was designed to evaluate the effect of ranitidine on pharmacokinetics of amoxicillin in the local population of Karachi, Pakistan. Amoxicillin and ranitidine are the most commonly prescribed drugs to treat duodenal ulcer caused by Helicobacter pylori. The current investigation was carried out as a single center, open label, two phase, single dose, randomized way in cross over manner to evaluate the potential of pharmacokinetic interaction among amoxicillin formulation and ranitidine in adult healthy male volunteers. Post dosing blood samples were collected at multiple time points that are 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 10 hours after administering amoxicillin 250mg capsule with and without ranitidine. For estimation of amoxicillin concentration in plasma, an HPLC method was developed and validated. The solvent system consisted of 0.025M phosphate buffer: acetonitrile (94:6 v/v). C18 column was employed with a flow rate of 1.0 ml/minute and at 230nm. A linear pattern with a correlation coefficient of 0.999 in the concentration ranges of 25μg/mL to 0.097μg/mL for amoxicillin and 25μg/mL to 0.048μg/mL for ranitidine was observed. Amoxicillin retention time was about 8 minutes and ranitidine retention time was around 12 minutes. Amoxicillin levels were computed and the concentrations were applied to calculate the pharmacokinetic parameters. Pharmacokinetic parameters were estimated by Kinetica TM 4.4.1 (Thermo Electron Corp. USA). The analysis of variance (two way) and t test (two one sided) were applied on log transformed pharmacokinetic parameters of amoxicillin. The Tmax was determined between amoxicillin alone and amoxicillin with ranitidine by Friedman test. The 90% confidence interval values for Cmax(calc) (0.687–0.743) and Tmax(calc) (1.148–1.742) for amoxicillin with or without ranitidine were not found within the FDA acceptable limits of 0.8–1.25. Study demonstrated the significant reduction in peak plasma levels of amoxicillin in presence of ranitidine. It is advisable to administer both drugs with time interval to avoid such interactions and increases in the bactericidal efficacy of amoxicillin.

Single and multiple oral amoxicillin treatment in geese: a pharmacokinetic evaluation

ABSTRACT 1. Although amoxicillin has broad-spectrum antibiotic activity and is extensively used in poultry, its use has never been investigated in geese. This study aimed to evaluate the pharmacokinetics of amoxicillin after a single and multiple oral doses in geese. 2. A total of 20 geese were enrolled in this study and randomly pooled in two groups (n = 10). In group I, animals were treated with a single oral 20 mg/kg dose of amoxicillin, while geese in group II were administered multiple doses (20 mg/kg/day for 4 d). Concentrations of amoxicillin in plasma were analysed using a validated HPLC-UV method and drug plasma concentrations were modelled for each subject using a non-compartmental approach. 3. amoxicillin showed rapid absorption after a single-dose treatment, with an elimination half-life of approximately 1 h. Cmax, Tmax and AUC values differed statistically between groups I and II (after the first dose administered). A large variability was observed in the pharmacokinetic profiles and drug accumulation may occur after the multiple administration. 4. No accumulation in plasma was predicted from an in-silico simulation performed using the same multiple dosage schedule. The in-silico simulation does not seem to accurately predict in-field conditions.

Pharmacokinetics and Bioequivalence of Two Amoxicillin 500mg Products: Effect of Food on Absorption and Supporting Scientific Justification for Biowaiver.

Aims of this study were to compare the bioequivalence of two formulations of amoxicillin 500mg capsules under fasted and fed conditions in the same set of healthy volunteers, compare pharmacokinetics of amoxicillin under the two conditions and to assess the possibility of predicting in vivo bioequivalence of the two formulations using in vitro dissolution data. The innovator product of amoxicillin was used as the reference formulation and a test product, which showed in vitro equivalence after a biowaiver study with the same reference product was used in the bioequivalence study. Altogether 16 subjects were randomized to the reference and test products in the fasted study and 12 of them participated in the fed study. Plasma concentration of amoxicillin was analyzed by a validated Liquid chromatography coupled with two mass spectrometry (LC-MS/MS) method. Noncompartmental analysis was used to determine the pharmacokinetic parameters. Average bioequivalence method was used to evaluate the bioequivalence of the two formulations and statistical significance of the pharmacokinetic parameters were tested to study the effect of food on amoxicillin absorption. The Geometric Mean Ratio (GMR) for the test/reference product for the maximum drug concentrations (Cmax) was 102.77% and 97.38% in fasted and fed conditions respectively which was within 80.00-125.00% range required to demonstrate bioequivalence. The GMR for test/reference products for the area under the curve (AUC0-8,) was 100.05% and 96.91% in fasted and fed conditions respectively meeting the bioequivalence criteria. For the reference product, the Cmax was 9.38 and 7.61µg x mL-1(p =0.0224), time to reach maximum concentration (Tmax) was 1.73 and 3.02h (p=0.0005) and AUC0-8 was 26.02 and 25.54µg/h-1mL-1p=0.672) under fasted and fed conditions respectively. The test and the reference formulations were bioequivalent under both fasted and fed conditions. Although the Cmax was significantly lower and Tmax was significantly delayed under fed conditions, it did not affect the AUC. Therefore, being a time dependent antibiotic, clinically significant effect of food on efficacy of amoxicillin is unlikely. As the selected products were equivalent in vitro, these findings support scientific justification for conducting in vitro dissolution studies for solid oral amoxicillin products as a surrogate for in vivo bioequivalence studies.

Pharmacokinetics of amoxicillin in obese and nonobese subjects.

To compare the pharmacokinetics of amoxicillin (AMX) in obese and nonobese subjects, given as single dose 875-mg tablets. A prospective, single-centre, open-label, clinical study was carried out involving 10 nonobese and 20 obese subjects given a dose of an AMX 875-mg tablet. Serial blood samples were collected between 0 and 8 hours after administration of AMX and plasma levels were quantified by liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameters (PK) were calculated by noncompartmental analysis and means of the 2 groups were compared using Student t-test. Analysis of correlation between covariates and PK was performed using Pearson's correlation coefficient. Ten nonobese subjects (mean age 30.6 ± 7.12 y; body mass index 21.56 ± 1.95 kg/m2 ) and 20 obese subjects (mean age 34.47 ± 7.03 y; body mass index 33.17 ± 2.38 kg/m2 ) participated in the study. Both maximum concentration (Cmax ; 12.12 ± 4.06 vs. 9.66 ± 2.93 mg/L) and area under the curve (AUC)0-inf (34.18 ± 12.94 mg.h/L vs. 26.88 ± 9.24 mg.h/L) were slightly higher in nonobese than in obese subjects, respectively, but differences were not significant. The volume of distribution (V/F) parameter was statistically significantly higher in obese compared to nonobese patients (44.20 ± 17.85 L vs. 27.57 ± 12.96 L). Statistically significant correlations were observed for several weight metrics vs. AUC, Cmax , V/F and clearance, and for creatinine clearance vs. AUC, Cmax and clearance. In obese subjects, the main altered PK was V/F as a consequence of greater body weight. This may result in antibiotic treatment failure if standard therapeutic regimens are administered.

Population Pharmacokinetics and Dosing Optimization of Amoxicillin in Chinese Infants.

Amoxicillin is used to treat various bacterial infections (eg, pneumonia, sepsis, meningitis) in infants. Despite its frequent use, there is a lack of population pharmacokinetic studies in infants, resulting in a substantial variability in dosing regimens used in clinical practice. Therefore, the objective of this study was to evaluate the population pharmacokinetics of intravenous amoxicillin in infants and suggest an optimal dosage regimen. Blood samples were collected for the determination of amoxicillin concentrations using an opportunistic sampling strategy. The amoxicillin plasma concentrations were determined using high-performance liquid chromatography. Population pharmacokinetic analysis was performed using NONMEM. A total of 62 pharmacokinetic samples from 47 infants (age range, 0.09 to 2.0 years) were available for analysis. A 2-compartment model with first-order elimination was most suitable to describe the population pharmacokinetics of amoxicillin, and covariate analysis showed that only current body weight was a significant covariate. Monte Carlo simulation demonstrated that the currently used dosage regimen (25mg/kg twice daily) resulted in only 22.4% of infants reaching their pharmacodynamic target, using a minimum inhibitory concentration (MIC) break point of 2mg/L, whereas a dosage regimen (60mg/kg thrice daily), as supported by the British National Formulary for Children, resulted in 80.9% of infants achieving their pharmacodynamic target. It is recommended to change antibiotics for infections caused by Escherichia coli (MIC= 8.0mg/L) because only 27.9% of infants reached target using 60mg/kg thrice daily.

Dose Rationale for Amoxicillin in Neonatal Sepsis When Referral Is Not Possible.

BackgroundDespite the widespread use of amoxicillin in young children, efforts to establish the feasibility of simplified dosing regimens in resource-limited settings have relied upon empirical evidence of efficacy. Given the antibacterial profile of beta-lactams, understanding of the determinants of pharmacokinetic variability may provide a more robust guidance for the selection of a suitable regimen. Here we propose a simplified dosing regimen based on pharmacokinetic-pharmacodynamic principles, taking into account the impact of growth, renal maturation and disease processes on the systemic exposure to amoxicillin.Materials and MethodsA meta-analytical modeling approach was applied to allow the adaptation of an existing pharmacokinetic model for amoxicillin in critically ill adults. Model parameterization was based on allometric concepts, including a maturation function. Clinical trial simulations were then performed to characterize exposure, as defined by secondary pharmacokinetic parameters (AUC, Cmax, Cmin) and T>MIC. The maximization of the T>MIC was used as criterion for the purpose of this analysis and results compared to current WHO guidelines.ResultsA two-compartment model with first order absorption and elimination was found to best describe the pharmacokinetics of amoxicillin in the target population. In addition to the changes in clearance and volume distribution associated with demographic covariates, our results show that sepsis alters drug distribution, leading to lower amoxicillin levels and longer half-life as compared to non-systemic disease conditions. In contrast to the current WHO guidelines, our analysis reveals that amoxicillin can be used as a fixed dose regimen including two weight bands: 125 mg b.i.d. for patients with body weight < 4.0 kg and 250 mg b.i.d. for patients with body weight ≥ 4.0 kg.ConclusionsIn addition to the effect of developmental growth and renal maturation, sepsis also alters drug disposition. The use of a model-based approach enabled the integration of these factors when defining the dose rationale for amoxicillin. A simplified weight-banded dosing regimen should be considered for neonates and young infants with sepsis when referral is not possible.

Pharmacokinetics of Amoxicillin and Cefepime During Prolonged Intermittent Renal Replacement Therapy: A Case Report

Prolonged intermittent renal replacement therapy (PIRRT) is an emerging form of renal replacement therapy in critically ill patients, but dosing data for antibiotics such as amoxicillin and cefepime are scarce and limited. This case report describes the effect of PIRRT on the plasma pharmacokinetics of amoxicillin and cefepime in a 69-year-old, critically ill patient with a polymicrobial intra-abdominal infection. Blood samples taken over 2 days, including a 7-hour PIRRT session, were analysed and a two-compartment model was used to describe cefepime and amoxicillin clearance and dosing requirements during PIRRT and off-PIRRT in this patient. Based on these data, an off-PIRRT dose of 1 g amoxicillin 12-hourly and cefepime 2 g daily with an on-PIRRT dose of 1 g amoxicillin 8-hourly and cefepime 2 g 12-hourly was deemed appropriate.

Amoxicillin in the treatment of acute respiratory infections in children: a dialogue between a microbiologist and a clinical pharmacologist

The article presents a modern view of amoxicillin in the treatment of acute respiratory infections in children from point of view of a microbiologist and clinical pharmacologist. Modern microbiological methods have changed the idea of the microbiota of the respiratory tract, however, the etiology of acute bacterial infections of the respiratory tract has not undergone significant changes – Streptococcus pneumoniae and Haemophilus influenzae are still the most common pathogens. Amoxicillin remains the drug of choice for most respiratory infections of bacterial etiology. Inhibitor-protected aminopenicillins (amoxicillin/clavulanate etc.) do not have advantages over amoxicillin in most cases of acute respiratory tract infections, but increase the risk of adverse events. Current data on macrolides, which are widely used in clinical practice, indicate the need to limit their use in acute infections of the respiratory tract due to the increase in resistance of S. pneumoniae and the absence of clinically significant activity against H. influenza. Current information on the resistance of S. pneumoniae and H. influenzae, as well as available data on the pharmacokinetics of amoxicillin, require a review of dosing approaches. The daily dose of amoxicillin in children with acute respiratory infections should not be less than 45–60 mg/kg, and in many cases (acute otitis media, infections caused by H. influenzae or penicillin-resistant S. pneumoniae strains), more than 90 mg/kg/day is required. Amoxicillin has a wide therapeutic range, and therefore the use of high doses of the drug is not associated with a decrease in the safety of therapy.

Pilot study of side effects and serum and urine concentrations of amoxicillin-clavulanic acid in azotemic and non-azotemic cats.

The aims of this study were to determine the side effect frequency and serum and urine drug concentrations of amoxicillin-clavulanic acid in cats with and without azotemic chronic kidney disease (azCKD). Owners whose cats had been prescribed amoxicillin-clavulanic acid completed a survey regarding the occurrence and type of side effects, and whether treatment was altered as a result. Cats were defined as azCKD (serum creatinine concentration >2.0 mg/dl, urine specific gravity [USG] <1.035 with a clinical diagnosis of chronic kidney disease) and without azCKD (serum creatinine concentration <2.0 mg/dl). Data were assessed with Fisher's exact test. Serum and urine samples were obtained from client-owned cats with azCKD (n = 6) and without azCKD (n = 6, serum creatinine concentration <1.8 mg/dl, USG >1.035) that were receiving amoxicillin-clavulanic acid. Amoxicillin and clavulanic acid were measured with liquid chromatography coupled to tandem mass spectrometry and compared between groups with a Mann-Whitney test. Correlation between serum creatinine and drug concentrations in urine and serum was determined using Spearman's rank test. Sixty-one surveys were returned (11 azCKD cats and 50 without azCKD cats). No significant difference in the presence of side effects or type of side effects was seen between groups; however, significantly more azCKD cats had more than one side effect (P = 0.02). More owners of azCKD cats reported that an alteration in treatment plan was necessitated by side effects (55% vs 12%; P = 0.008). Urine amoxicillin was significantly lower in cats with azCKD (P = 0.01) and serum amoxicillin trended toward significance (P = 0.07). Serum amoxicillin concentration was positively correlated with serum creatinine (P = 0.02; r = 0.62) and urine amoxicillin concentration was negatively correlated with serum creatinine (P = 0.01; r = -0.65). The data suggest that cats with azCKD have altered pharmacokinetics of amoxicillin, which may contribute to an increased incidence of multiple side effects.

A rapid, simple and sensitive liquid chromatography tandem mass spectrometry assay to determine amoxicillin concentrations in biological matrix of little volume

To assess pharmacokinetics of amoxicillin (AMX) in mice, limitations such as a small sampling volume and low drug concentrations have to be addressed. Similar challenges are faced in a clinical framework, e.g. for therapeutic drug monitoring in neonates or small-scale in vitro investigations. An assay enabling quantification of small sample volumes but still at very low concentrations covering a broad concentration range is thus needed.A simple, rapid and highly sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed and successfully validated for quantification of AMX in mouse serum according to European Medicines Agency guidelines. Sample preparation enabled the use of only 10 μL of serum, which is 5-fold less than comparable assays and allows to reduce the number of mice used in pharmacokinetic studies. After protein precipitation with 40 μL chilled methanol and dilution of the supernatant with water, the sample was injected into the LC system on a Poroshell 120 Phenyl Hexyl column (2.1 × 100 mm, 2.7 μm). Chromatographic separation was achieved using a gradient method consisting of acetonitrile and ultra-pure water, both with 0.1% (V/V) formic acid. Positive electrospray ionisation in multiple reaction monitoring mode was used for detection and quantification of AMX. Application to murine study samples demonstrated the reliability of the developed method being accurate and precise with a quantification range from 0.01 to 10 μg/mL. The assay is easily transferable due to a simple sample preparation and confirmed stability of AMX under various applied conditions.

Population Pharmacokinetics and Dosing Optimization of Amoxicillin in Neonates and Young Infants.

Amoxicillin is widely used to treat bacterial infections in neonates. However, considerable intercenter variability in dosage regimens of antibiotics exists in clinical practice. The pharmacokinetics of amoxicillin has been described in only a few preterm neonates. Thus, we aimed to evaluate the population pharmacokinetics of amoxicillin through a large sample size covering the entire age range of neonates and young infants and to establish evidence-based dosage regimens based on developmental pharmacokinetics-pharmacodynamics. This is a prospective, multicenter, pharmacokinetic study using an opportunistic sampling design. Amoxicillin plasma concentrations were determined using high-performance liquid chromatography. Population pharmacokinetic analysis was performed using NONMEM. A total of 224 pharmacokinetic samples from 187 newborns (postmenstrual age range, 28.4 to 46.3 weeks) were available for analysis. A two-compartment model with first-order elimination was used to describe population pharmacokinetics. Covariate analysis showed that current weight, postnatal age, and gestational age were significant covariates. The final model was further validated for predictive performance in an independent cohort of patients. Monte Carlo simulation demonstrated that for early-onset sepsis, the currently used dosage regimen (25 mg/kg twice daily [BID]) resulted in 99.0% of premature neonates and 87.3% of term neonates achieving the pharmacodynamic target (percent time above MIC), using a MIC breakpoint of 1 mg/liter. For late-onset sepsis, 86.1% of premature neonates treated with 25 mg/kg three times a day (TID) and 79.0% of term neonates receiving 25 mg/kg four times a day (QID) reached the pharmacodynamic target, using a MIC breakpoint of 2 mg/liter. The population pharmacokinetics of amoxicillin was assessed in neonates and young infants. A dosage regimen was established based on developmental pharmacokinetics-pharmacodynamics.

Impact of Bariatric Surgery on the Pharmacokinetics Parameters of Amoxicillin.

Bariatric surgery leads to several anatomo-physiological modifications that may affect pharmacokinetic parameters and consequently alter the therapeutic effect of drugs, such as antibiotics. The pharmacokinetics of oral amoxicillin after Roux-en-Y gastric bypass (RYGB) surgery is unknown. The objective of this study was to evaluate the impact of bariatric surgery on the pharmacokinetics of amoxicillin. This study was performed as a randomized, open-label, single-dose clinical trial, with two periods of treatment, in which obese subjects (n = 8) received an amoxicillin 500mg capsule orally before and 2months after the RYGB surgery. The amoxicillin plasma concentration was determined by liquid chromatography coupled to mass spectrometry (LC-MS/MS). After the surgery, the mean weight loss was 17.03 ± 5.51kg, and mean body mass index (BMI) decreased from 46.21 ± 2.82 to 38.82 ± 3.32kg/m2. The mean amoxicillin area under the plasma concentration versus time curve from time zero to the time of the last quantifiable concentration (AUC0-tlast) increased significantly (3.5-fold); the maximum plasma concentration (Cmax) increased 2.8-fold after the bariatric surgery. No correlation was found between amoxicillin absorption, BMI, and weight loss percentage. The alterations observed in the amoxicillin pharmacokinetics suggest that obese subjects included in this trial had a substantially increase in amoxicillin systemic exposure after RYGB surgery. However, despite this increase, its exposure was lower than the values reported for non-obese volunteers. Identifiers: NCT03588273.

Determination of milk/plasma ratio and milk and plasma pharmacokinetics of amoxicillin after intramuscular administration in lactating cows.

This study was conducted to determine the passage ratio of amoxicillin into milk and its pharmacokinetics in milk and plasma after intramuscular administration. Five healthy dairy cows (Holstein, weighing 450-500kg, aged 2-4years) were used in this study. They received single intramuscular amoxicillin at a dose of 14mg/kg body weight. Blood and milk samples were collected prior to drug administration (0); after 15, 30, 45, 60, and 90min; and 2, 3, 4, 6, 8, 10, and 12hr after administration. The plasma and milk concentrations of amoxicillin were determined using high-performance liquid chromatography with ultraviolet detection. The passage ratio of amoxicillin into milk and plasma was determined using both AUC-based calculation and milk and plasma concentrations at sampling times; it was calculated 0.46 and 0.52, respectively. The terminal half-life and mean residence time of amoxicillin were 6.05 and 8.60hr in plasma and 2.62 and 5.35hr in milk, respectively. The Cmax2 levels of amoxicillin in plasma and milk were measured as 1,096 and 457ng/ml, respectively. It was observed that amoxicillin exhibited a secondary peak in plasma and milk. This study was the first to report on the passage ratio of amoxicillin into milk in lactating cows.

Efficacy of Reduced Dosage of Amoxicillin in an Eradication Therapy for Helicobacter pylori Infection in Patients on Hemodialysis: A Randomized Controlled Trial

Background: An optimum Helicobacter pylori-eradication regimen for hemodialysis patients is yet to be established because of different pharmacokinetics of amoxicillin involved between hemodialysis patients and healthy subjects. We investigated to establish appropriate doses of amoxicillin for H. pylori infection eradication in hemodialysis patients. Methods: Of 409 hemodialysis patients screened for H. pylori infection, 37 H. pylori-positive patients were randomized to different 1-week eradication regimens: esomeprazole 20 mg twice a day (b.i.d.) and clarithromycin 200 mg b.i.d., plus amoxicillin at either 750 mg b.i.d. (group A; conventional) or 250 mg b.i.d. (group B; experimental). Sixty-three patients with normal renal function received the conventional regimen (group C). Successful eradication was confirmed by urea breath testing. Results: Eradication rates of group B (reduced amoxicillin-regimen) were 84.2% in intention-to-treat analysis and 88.9% in per-protocol analysis, which were similar with group A (77.8 and 77.8%) and group C (74.6 and 81.0%). However, the incidence of adverse events in group A was significantly higher than that in group C (22.2 vs. 5.1%, p = 0.027). Conclusions: In H. pylori-positive hemodialysis patients, amoxicillin at 250 mg b.i.d. may be an appropriate scheme for eradication with equivalent effects to the conventional therapy and safety effects for adverse events.

The influence of growth and E. coli endotoxaemia on amoxicillin pharmacokinetics in turkeys

ABSTRACT1. This experiment aimed to determine if the pharmacokinetics of amoxicillin (AMO) was affected by rapid growth or intravenous (i.v.) injection of Escherichia coli lipopolysaccharide (LPS).2. Turkeys of 2.0, 5.5 and 12.0 kg were administered i.v. or orally with AMO sodium at the dose of 15 mg/kg. Another group (5.7 kg) was treated with LPS prior to i.v. AMO administration. Plasma drug concentrations were determined using high-performance liquid chromatography and pharmacokinetic parameters were calculated using a non-compartmental model. To assess the haemodynamic effects of endotoxaemia, turkeys were subjected to echocardiography.3. During growth from 2.0 to 5.5 kg, the area under the drug concentration-time curve after i.v. AMO administration increased from 9.37 ± 2.43 to 21.29 ± 5.49 mg×h/ml. Total body clearance decreased from 1.72 ± 0.55 to 0.75 ± 0.12 l/h/kg. Growth to 12.0 kg did not further affect these parameters. Mean residence time and elimination half-life gradually increased. Pharmacokinetics of orally administered drug followed a similar pattern. LPS injection affected stroke volume, heart rate and resistance index. However, it did not affect the pharmacokinetic profile of AMO in survivors.4. It is concluded that rapid growth in turkeys affects AMO pharmacokinetics. Endotoxaemia, on the other hand, does not affect AMO elimination if compensatory mechanisms develop.

Non-linear absorption pharmacokinetics of amoxicillin: consequences for dosing regimens and clinical breakpoints.

To describe the population pharmacokinetics of oral amoxicillin and to compare the PTA of current dosing regimens. Two groups, each with 14 healthy male volunteers, received oral amoxicillin/clavulanic acid tablets on two separate days 1 week apart. One group received 875/125 mg twice daily and 500/125 mg three times daily and the other group 500/125 mg twice daily and 250/125 mg three times daily. A total of 1428 amoxicillin blood samples were collected before and after administration. We analysed the concentration-time profiles using a non-compartmental pharmacokinetic method (PKSolver) and a population pharmacokinetic method (NONMEM). The PTA was computed using Monte Carlo simulations for several dosing regimens. AUC0-24 and Cmax increased non-linearly with dose. The final model included the following components: Savic's transit compartment model, Michaelis-Menten absorption, two distribution compartments and first-order elimination. The mean central volume of distribution was 27.7 L and mean clearance was 21.3 L/h. We included variability for the central volume of distribution (34.4%), clearance (25.8%), transit compartment model parameters and Michaelis-Menten absorption parameters. For 40% fT>MIC and >97.5% PTA, the breakpoints were 0.125 mg/L (500 mg twice daily), 0.25 mg/L (250 mg three times daily and 875 mg twice daily), 0.5 mg/L (500 mg three times daily) and 1 mg/L (750, 875 or 1000 mg three times daily and 500 mg four times daily). The amoxicillin absorption rate appears to be saturable. The PTAs of high-dose as well as twice-daily regimens are less favourable than regimens with lower doses and higher frequency.

阿莫西林脉冲微丸的释药机制及其药动学研究

阿莫西林脉冲微丸的释药机制及其药动学研究

EVALUATION OF AMOXICILLIN WITHDRAWAL PERIOD TIME IN POMPANO LIVER AND KIDNEY

Amoxicillin is an antibiotic which belongs to the group of penicillins. It is approved in Taiwan for treating bacterial infections caused by Streptococcus sp. and Photobacterium sp. in anguilliformes, perciformes and salmoniformes. The pharmacokinetics of amoxicillin were determined in pompano following oral administration of a single dose of 40 mg/kg. Residue studies were performed to determine residues in liver and kidney tissues of healthy fish after oral gavage of amoxicillin at a daily dose of 40 mg/kg for five consecutive days. Amoxicillin residues were analyzed by HPLC using Hypersil-100 C18 column (150 mm × 4.6 mm i.d.) and mobile phase consists of 10 mM K2HPO4(pH 8.5) with acetonitrile (80:20, v/v), at a flow rate of 1 mL/min. The effluent was monitored using a fluorescence detector set as 358 and 440 nm as excitation and emission wavelengths. Following a single oral dose, amoxicillin residues in 0.5 h post-dosing pompano were at a maximum of 6.17 μg/g in liver and 4.27 μg/g in kidney; the concentration of amoxicillin in liver and kidney declined with half-lives of 18.3 and 12.0 h. Amoxicillin residues in pompano liver and kidney tissues were proved to be under the MRL, 0.5 ug/g (liver and kidney) after a withdrawal period of five days.

ESTIMATION OF THE WITHDRAWAL PERIOD FOR AMOXICILLIN IN POMPANO (TRACHINOTUS BLOCHII) SERUM AND MUSCLE

Amoxicillin is one of the most popular antibiotics used in aquaculture. To ensure the residue of amoxicillin in the serum and the muscle of pompano (Trachinotus blochii) is below the established tolerance levels; we used reversed phase high-performance liquid chromatography (HPLC) to measure the amoxicillin in pompano after oral administration. The pharmacokinetics of amoxicillin in the serum and the muscle of pompano were established by single oral administration or administrations for five consecutive days at the dose of 40 mg/kg. After different depletion periods, amoxicillin residue was analyzed in both the serum and the muscle fillets by HPLC. The verified concentrations of this method were 0.01 to 10 μg/mL; the limit of detection (LOD) and the limit of quantitation (LOQ) were 0.04 and 0.1 μg/g. The concentration of amoxicillin in the serum of pompano reached the maximum threshold of 7.36 μg/g after 0.5 h depletion in the experiment with a single dose of amoxicillin (40 mg/kg of body weight). In addition, the maximal concentration (1.96 μg/g) of amoxicillin was detected in the muscle 2 h after depletion. Furthermore, the residue levels had decreased below the limit of detection after 48 h and 72 h in the serum and the muscle. Here we also suggested that 5 days of withdrawal were required after the multiple dosing of amoxicillin.