scholarly journals Pharmacokinetic Study of Amoxicillin Capsule in Healthy Bangladeshi Subjects using Urinary Excretion Data

1970 ◽  
Vol 8 (1) ◽  
pp. 53-59 ◽  
Author(s):  
Md Ashik Ullah ◽  
Mohammad Abul Kalam Azad ◽  
Rebeka Sultana ◽  
Eva Rahman Kabir ◽  
AHM Mahbub Latif ◽  
...  
Keyword(s):  
Urinary Excretion ◽  
Drug Disposition ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Ethnic Variation ◽  
Open Label ◽  
Time Intervals ◽  
Significant Difference ◽  
The Us ◽  
The Mean

The aim of the study was to compare the urinary excretion data and bioavailability of two 500 mgamoxicillin capsules formulations in healthy Bangladeshi subjects under fasting condition and evaluate the ethnicvariations in drug disposition. Twenty-four subjects were enrolled into this single-dose, randomized, open-label, twowaycross over study. A washout period of one week was allowed between two treatments. Following oraladministration, urine samples were collected at different time intervals and were analyzed using a validated HPLCmethod with UV detection. The pharmacokinetic parameters for two formulations were calculated by noncompartmentalmethod using the software Kinetica and statistical analysis was done for the evaluation ofbioequivalence. The pharmacokinetic analysis indicated that the kinetic disposition of two formulations was similar.This was evident when the mean (± standard deviation) values of the various pharmacokinetic parameters werecompared. No significant difference between two formulations was found when analyzed by paired t-test andANOVA. Therefore it can be concluded that the test product (SK-mox®) is bioequivalent to the reference product(Amoxil-Bencard®) based on the US FDA's regulatory definition. Moreover, an ethnic variation was observedfollowing 64.34% cumulative urinary recovery of amoxicillin over 12 hours when compared with other studies.Key words: Amoxicillin; pharmacokinetics; Bangladeshi subjects.DOI: 10.3329/dujps.v8i1.5336Dhaka Univ. J. Pharm. Sci. 8(1): 53-59, 2009 (June)

A COMPARISON OF TWO METHODS FOR MEASUREMENT OF ALDOSTERONE SECRETION RATE IN MAN

1966 ◽  
Vol 53 (2) ◽  
pp. 177-188 ◽  
Author(s):  
P. Lund-Johansen ◽  
T. Thorsen ◽  
K. F. Støa
Keyword(s):  
Urinary Excretion ◽  
Normal Subjects ◽  
Secretion Rate ◽  
Aldosterone Secretion ◽  
Simple Method ◽  
Mean Values ◽  
Pathological Conditions ◽  
Significant Difference ◽  
Derivative Method ◽  
The Mean

ABSTRACT A comparison has been made between (A), a relatively simple method for the measurement of aldosterone secretion rate, based on paper chromatography and direct densitometry of the aldosterone spot and (B) a more elaborate isotope derivative method. The mean secretion rate in 9 normal subjects was 112 ± 26 μg per 24 hours (method A) and 135 ± 35 μg per 24 hours (method B). The »secretion rate« in one adrenalectomized subject after the intravenous injection of 250 μg of aldosterone was 230 μg per 24 hours (method A) and 294 μg per 24 hours (method B). There was no significant difference in the mean values, and correlation between the two methods was good (r = 0.80). It is concluded that the densitometric method is suitable for clinical purposes as well as research, being more rapid and less expensive than the isotope derivative method. Method A also measures the urinary excretion of the aldosterone 3-oxo-conjugate, which is of interest in many pathological conditions. The densitometric method is obviously the less sensitive and a prerequisite for its use is an aldosterone secretion of 20—30 μg per 24 hours. Lower values are, however, rare in adults.

scholarly journals Ethnic variation in medial orbital wall anatomy and its implications for decompression surgery

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Minhui Amy Chan ◽  
Farah Ibrahim ◽  
Arjunan Kumaran ◽  
Kailing Yong ◽  
Anita Sook Yee Chan ◽  
...  
Keyword(s):  
Relative Position ◽  
Ethmoid Sinus ◽  
Decompression Surgery ◽  
Ethnic Variation ◽  
Sinus Wall ◽  
Orbital Wall ◽  
Mean Width ◽  
Significant Difference ◽  
The Mean ◽  
Medial Orbital Wall

Abstract Background To describe the inter-ethnic variation in medial orbital wall anatomy between Chinese, Malay, Indian and Caucasian subjects. Methods Single-centre, retrospective, Computed Tomography (CT)-based observational study. 20 subjects of each ethnicity, were matched for gender and laterality. We excluded subjects younger than 16 years and those with orbital pathology. OsiriX version 8.5.1 (Pixmeo., Switzerland) and DICOM image viewing software CARESTREAM Vue PACS (Carestream Health Inc., USA) were used to measure the ethmoidal sinus length, width and volume, medial orbital wall and floor angle and the relative position of the posterior ethmoid sinus to the posterior maxillary wall. Statistical analyses were performed using Statistical Package for Social Sciences version 25.0 (IBM, USA). Results There were 12 males (60 %) in each group, with no significant difference in age (p = 0.334–0.994). The mean ethmoid sinus length in Chinese, Malay, Indian and Caucasian subjects, using the Chinese as reference, were 37.2, 36.9, 38.0 and 37.4mm, the mean width was 11.6, 10.5, 11.4 and 10.0mm (p = 0.020) and the mean ethmoid sinus volume were 3362, 3652, 3349 and 3898mm3 respectively. The mean medial orbital wall and floor angle was 135.0, 131.4, 131.0 and 136.8 degrees and the mean relative position of posterior ethmoid sinus to posterior maxillary wall were − 2.0, -0.2, -1.5 and 1.6mm (p = 0.003) respectively. Conclusions No inter-ethnic variation was found in decompressible ethmoid sinus volume. Caucasians had their posterior maxillary sinus wall anterior to their posterior ethmoidal walls unlike the Chinese, Malay and Indians. Awareness of ethnic variation is essential for safe orbital decompression.

scholarly journals THU0410 COMPANION IMMUNOSUPPRESSION WITH AZATHIOPRINE INCREASES THE FREQUENCY OF PERSISTENT RESPONSIVENESS TO PEGLOTICASE IN PATIENTS WITH CHRONIC REFRACTORY GOUT

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 442.2-443 ◽  
Author(s):  
H. Rainey ◽  
H. S. B. Baraf ◽  
A. Yeo ◽  
P. Lipsky
Keyword(s):  
Serum Urate ◽  
Infusion Reaction ◽  
Blood Levels ◽  
Open Label ◽  
Methyl Transferase ◽  
The Us ◽  
The Mean ◽  
Artery Disease ◽  
Metabolizing Enzyme ◽  
Gout Flares

Background:Pegloticase is a mammalian recombinant uricase coupled to monomethoxy polyethylene glycol that is approved in the US for treatment of patients with chronic refractory gout and causes profound reductions in serum urate. However, treatment with pegloticase is limited by the induction of anti-drug antibodies and loss of responsiveness in nearly half of treated patients.Objectives:The goal of this study was to determine whether co-therapy with azathioprine (AZA) would increase the frequency of chronic refractory gout patients who had persistent urate lowering from pegloticase therapy.Methods:This open label multicenter study enrolled subjects with chronic gout who failed to lower serum urate to <6 mg/dL despite medically indicated doses of urate lowering therapy (NCT02598596). Patients were screened for adequate levels of the AZA metabolizing enzyme thiopurine methyl transferase and then started on daily oral AZA 1.25 mg/kg for 1 week and then 2.5 mg/kg for the remainder of the trial. Blood levels of AZA metabolites 6-thioguanine and 6-methylmercaptopurine were measured biweekly. After receiving 2 weeks of AZA, patients were started on pegloticase (8 mg IV) and were treated biweekly for 24 weeks. The primary endpoint was the persistent lowering of serum urate to <6 mg/dL at the last three consecutive study visits. Patients who had an increase in serum urate to >6 mg/dL while on therapy did not receive additional pegloticase. All patients received infusion prophylaxis with hydrocortisone as well as gout flare prophylaxis.Results:To date, 12 patients have been enrolled. All patients were male, 75% white and 25% African American. Mean age was 62.4 ± 14.7 years, the mean BMI was 31.1 ± 4.5 and the mean duration of gout was 13.8 ± 9.2 years. At baseline, all patients had visible tophi; 58.3% suffered from gout flares; 81.8% had hypertension; 45.5% had dyslipidemia and 9.0% had coronary artery disease. Of the 12 patients, 6 have completed the full course of treatment with persistent urate lowering and 2 remain on treatment also with persistent urate lowering (figure). 2 patients lost the urate lowering effect, both after 2 doses of pegloticase, and did not receive additional therapy. 1 patient experienced an infusion reaction during the first dose (1 infusion reaction in 90 infusions [1.1%] in the entire trial to date) and 1 subject had subjective symptoms of AZA intolerance with no laboratory abnormalities; these subjects discontinued the study and were not evaluable for the endpoint. No adverse events related to AZA were reported and gout flares were noted in 6 subjects (mean 1.5 flares/patient with flares).Conclusion:AZA can be used safely in subjects with chronic refractory gout and appears to increase the frequency of subjects experiencing long term lowering of serum urate.References:Disclosure of Interests: :Hope Rainey: None declared, Herbert S.B. Baraf Grant/research support from: Horizon; Gilead Sciences, Inc.; Pfizer; Janssen; AbbVie, Consultant of: Horizon; Gilead Sciences, Inc.; Merck; AbbVie, Speakers bureau: Horizon, Anthony Yeo Employee of: Horizon, Peter Lipsky Consultant of: Horizon Therapeutics

Insulin Glargine and Risk of Cancer: A Meta-Analysis

2012 ◽  
Vol 27 (3) ◽  
pp. 241-246 ◽  
Author(s):  
Xinli Du ◽  
Rihua Zhang ◽  
Yi Xue ◽  
Dong Li ◽  
Jinmei Cai ◽  
...  
Keyword(s):  
Insulin Glargine ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Long Term Effects ◽  
Open Label ◽  
Cancer Occurrence ◽  
Pubmed Database ◽  
Significant Difference ◽  
The Us ◽  
Risk Of Cancer

Aims Recently, more and more attention has been drawn on the long-term effects of insulin glargine. Here we strived to estimate the association of cancer occurrence with the use of insulin glargine. Methods We searched all the publications regarding the association between cancer occurrence and the use of insulin glargine using the US National Library of Medicine's PubMed database. Data were independently extracted and analyzed using random or fixed effects meta-analysis depending upon the degree of heterogeneity. Results Seven cohort studies were included in the meta-analysis. Cancer occurrence had no significant difference in glargine-treated patients compared to patients treated with other insulins (RR=0.86, 95% CI=0.69–1.07, p=0.17, Pheterogeneity <0.00001). In our subgroup analysis, glargine, compared to other insulins, did not increase the risk of breast cancer (RR=1.14, 95% CI=0.65–2.02, p=0.65, Pheterogeneity=0.002), prostate cancer (RR=1.00, 95% CI=0.79–1.26, p=0.99, Pheterogeneity=0.78), pancreatic cancer (RR=0.57, 95% CI=0.14–2.35, p=0.44, Pheterogeneity=0.0002) and gastrointestinal cancer (RR=0.80, heterogeneity 95% CI=0.62–1.02, p=0.07, Pheterogeneity=0.86). Conclusions This meta-analysis of open-label studies does not support an increased cancer risk in patients treated with insulin glargine. The result provides confidence for the development of insulin glargine, but needs confirmation by further clinical studies.

Rectal Administration of Ibuprofen: Comparison of Enema and Suppository Form

Drug Research ◽  
2021 ◽  
Author(s):  
Budi Prasaja ◽  
Yahdiana Harahap ◽  
Monika Sandra ◽  
Irene Iskandar ◽  
Windy Lusthom ◽  
...  
Keyword(s):  
Phase 1 ◽  
Rectal Administration ◽  
Pharmacokinetic Parameters ◽  
P Value ◽  
Open Label ◽  
Post Dose ◽  
Anova Model ◽  
Equal Dose ◽  
Rate Of Absorption ◽  
The Mean

AbstractIbuprofen is a widely used and well-tolerated analgesic and antipyretic. It is desirable to have a formulation with a rapid rate of absorption because it is required for rapid pain relief and temperature reduction. Previous studies have described the pharmacokinetic profiles of ibuprofen suppository and the mean peak times of ibuprofen suppository were around 1.8 hours, indicating a slower rate of absorption. The aim of this study is to compare the pharmacokinetic parameters of rectal administration of ibuprofen between enema and suppository form in order to provide evidence for the faster absorption rates of ibuprofen enema. This study was a phase-1 clinical study, open-label, randomized and two-way crossover with one-week washout period comparing the absorption profile of equal dose of ibuprofen administered rectally in two treatment phases: ibuprofen suppository and enema. Blood samples were collected post dose for pharmacokinetic analyses. Tmax was analyzed using a Wilcoxon matched paired test. A standard ANOVA model, appropriate for bioequivalence studies was used and ratios of 90% confidence intervals were calculated. This study showed that Tmax for ibuprofen enema was less than half that of ibuprofen suppository (median 40 min vs. 90 min, respectively; p-value=0.0003). Cmax and AUC0–12 for ibuprofen enema were bioequivalent to ibuprofen suppository, as the ratio of test/reference=104.52%, 90% CI 93.41–116.95% and the ratio of test/reference=98.12%, 90%CI 93.34–103.16%, respectively, which fell within 80–125% bioequivalence limit. The overall extent of absorption was similar to the both, which were all well tolerated. In terms of Tmax, Ibuprofen enema was absorbed twice as quickly as from ibuprofen suppository. Therefore it is expected that an ibuprofen enema may provide faster onset of analgesic and antipyretic benefit.

scholarly journals Population Pharmacokinetic Analysis of Vancomycin Using Serum Cystatin C as a Marker of Renal Function

2009 ◽  
Vol 54 (2) ◽  
pp. 778-782 ◽  
Author(s):  
Akihiro Tanaka ◽  
Tetsuya Aiba ◽  
Takashi Otsuka ◽  
Katsuya Suemaru ◽  
Tatsuya Nishimiya ◽  
...  
Keyword(s):  
Renal Function ◽  
Cystatin C ◽  
Predictive Performance ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Population Pharmacokinetic ◽  
Serum Cystatin C ◽  
Serum Cystatin ◽  
New Model ◽  
The Mean

ABSTRACT We determined the population pharmacokinetics of vancomycin (VAN) using the glomerular filtration rate (GFR) estimated from the serum cystatin C concentration. We examined the predictive performance of the trough serum VAN concentration for determination of the initial dose by using a new model for the analysis of the population pharmacokinetic parameters. Data for 86 patients were used to estimate the values of the population pharmacokinetic parameters. Analysis with a nonlinear mixed-effects modeling program was done by using a one-compartment model. Data for 78 patients were used to evaluate the predictive performance of the new model for the analysis of population pharmacokinetic parameters. The estimated GFR values determined by using Hoek's formula correlated linearly with VAN clearance (VAN clearance [ml/min] = 0.825 × GFR). The mean volume of distribution was 0.864 (liters/kg). The interindividual variability of VAN clearance was 19.8%. The accuracy of the prediction determined by use of the new model was statistically better than that determined by use of the Japanese nomogram-based model because the 95% confidence interval (−3.45 to −1.38) of the difference in each value of the mean absolute error (−2.41) did not include 0. Use of the serum cystatin C concentration as a marker of renal function for prediction of serum VAN concentrations may be useful.

Urinary excretion of glycated protein determined with a specific radioimmunoassay

1991 ◽  
Vol 37 (4) ◽  
pp. 504-507 ◽  
Author(s):  
Chizuko Ukita ◽  
Mitsushige Nishikawa ◽  
Akira Shouzu ◽  
Mitsuo Inada
Keyword(s):  
Urinary Excretion ◽  
Normal Subjects ◽  
Mean Values ◽  
Specific Radioimmunoassay ◽  
Glycated Protein ◽  
Highly Sensitive ◽  
Significant Difference ◽  
Group A ◽  
The Mean ◽  
Group B

Abstract We developed a simple and highly sensitive RIA for glycated protein (GP), and used it to measure GP in serum and urine from 15 normal controls and 30 diabetics (14 with urinary excretion rate of albumin, Ualb less than 15 micrograms/min, group A; nine with 15 less than or equal to Ualb less than or equal to 150 micrograms/min, group B; and seven with Ualb greater than 150 micrograms/min, group C). The mean serum concentration of GP was above normal in all groups of diabetics, and the mean glycation ratios of serum protein (SGP) were higher in groups B and C than in normal subjects. Urinary concentrations of GP also were increased in groups B and C, although the glycation ratio of urinary protein (UGP) was decreased in group C. Consequently, the selectivity of urinary excretion of GP (UGP/SGP) was significantly decreased in group C. Moreover, there was a significant difference in the mean values of selectivity between groups of patients with various degrees of retinopathy. We suggest that measurements of serum and urinary GP are useful to evaluate the progression of diabetic complications.

scholarly journals Joint Population Pharmacokinetic Analysis of Zidovudine, Lamivudine, and Their Active Intracellular Metabolites in HIV Patients

2011 ◽  
Vol 55 (7) ◽  
pp. 3423-3431 ◽  
Author(s):  
C. Bazzoli ◽  
H. Bénech ◽  
E. Rey ◽  
S. Retout ◽  
D. Salmon ◽  
...  
Keyword(s):  
Compartment Model ◽  
Population Pharmacokinetic Analysis ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Population Pharmacokinetic ◽  
Intracellular Metabolites ◽  
Drug Concentrations ◽  
The Mean ◽  
Intracellular Concentrations ◽  
Apparent Bioavailability

ABSTRACTThe population pharmacokinetic parameters of zidovudine (AZT), lamivudine (3TC), and their active intracellular metabolites in 75 naïve HIV-infected patients receiving an oral combination of AZT and 3TC twice daily as part of their multitherapy treatment in the COPHAR2-ANRS 111 trial are described. Four blood samples per patient were taken after 2 weeks of treatment to measure drug concentrations at steady state. Plasma AZT and 3TC concentrations were measured in 73 patients, and among those, 62 patients had measurable intracellular AZT-TP and 3TC-TP concentrations. For each drug, a joint population pharmacokinetic model was developed and we investigated the influence of different covariates. We then studied correlations between the mean plasma and intracellular concentrations of each drug. A one-compartment model with first-order absorption and elimination best described the plasma AZT concentration, with an additional compartment for intracellular AZT-TP. A similar model but with zero-order absorption was found to adequately described concentrations of 3TC and its metabolite 3TC-TP. The half-lives of AZT and 3TC were 0.81 h (94.8%) and 2.97 h (39.2%), respectively, whereas the intracellular half-lives of AZT-TP and 3TC-TP were 10.73 h (69%) and 21.16 h (44%), respectively. We found particularly a gender effect on the apparent bioavailability of AZT, as well as on the mean plasma and intracellular concentrations of AZT, which were significantly higher in females than in males. Relationships between mean plasma drug and intracellular metabolite concentrations were also highlighted both for AZT and for 3TC. Simulation with the model of plasma and intracellular concentrations for once- versus twice-daily regimens suggested that a daily dosing regimen with double doses could be appropriate.

scholarly journals Phenotypic differences in nebivolol metabolism and bioavailability in healthy volunteers

2015 ◽  
Vol 88 (2) ◽  
pp. 208-213 ◽  
Author(s):  
Corina Briciu ◽  
Maria Neag ◽  
Dana Muntean ◽  
Corina Bocsan ◽  
Anca Buzoianu ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Active Metabolite ◽  
Genetic Regulation ◽  
Standard Normal Distribution ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Open Label ◽  
Phenotypic Differences ◽  
Standard Normal ◽  
Unique Distribution

Introduction: Nebivolol, a third-generation β-blocker, is subject to extensive first-pass metabolism and produces active β-blocking hydroxylated metabolites, like 4-OH-nebivolol. It is primarily a substrate of CYP2D6, a metabolic pathway that is under polymorphic genetic regulation. The objective of this study was to assess the metabolizer phenotype and to evaluate the interphenotype bioavailability and metabolism of nebivolol.Material and methods: Forty-three healthy volunteers were included in this open-label, non-randomized clinical trial and each volunteer received a single dose of 5 mg nebivolol. Non-compartmental pharmacokinetic analysis was performed to determine the pharmacokinetic parameters of nebivolol and its active metabolite. The phenotypic distribution was assessed based on the AUC (aria under the curve) metabolic ratio of nebivolol/4-OH-nebivolol and statistical analysis. An interphenotype comparison of nebivolol metabolism and bioavailability was performed based on the pharmacokinetic parameters of nebivolol and its active metabolite.Results: Nebivolol/4-OH-nebivolol AUC metabolic ratios were not characterized by a standard normal distribution. The unique distribution emphasized the existence of two groups and the 43 healthy volunteers were classified as follows: poor metabolizers (PMs)=3, extensive metabolizers (EMs)=40. The phenotype had a marked impact on nebivolol metabolism. The exposure to nebivolol was 15-fold greater for PMs in comparison to EMs.  Conclusion: 40 EMs and 3 PMs were differentiated by using the pharmacokinetic parameters of nebivolol and its active metabolite. The study highlighted the existence of interphenotype differences regarding nebivolol metabolism and bioavailability.

scholarly journals Extended-Interval Gentamicin Dosing in Achieving Therapeutic Concentrations in Malaysian Neonates

2015 ◽  
Vol 20 (2) ◽  
pp. 119-127
Author(s):  
Yee Shan Low ◽  
Sin Li Tan ◽  
Angeline SL Wan
Keyword(s):  
Body Weight ◽  
Gestational Age ◽  
Trough Concentration ◽  
Elimination Rate ◽  
Dose Interval ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Creatinine Concentration ◽  
Cross Sectional ◽  
Significant Difference

OBJECTIVE: To evaluate the usefulness of extended-interval gentamicin dosing practiced in neonatal intensive care unit (NICU) and special care nursery (SCN) of a Malaysian hospital. METHODS: Cross-sectional observational study with pharmacokinetic analysis of all patients aged ≤28 days who received gentamicin treatment in NICU/SCN. Subjects received dosing according to a regimen modified from an Australian-based pediatric guideline. During a study period of 3 months, subjects were evaluated for gestational age, body weight, serum creatinine concentration, gentamicin dose/interval, serum peak and trough concentrations, and pharmacokinetic parameters. Descriptive percentages were used to determine the overall dosing accuracy, while analysis of variance (ANOVA) was conducted to compare the accuracy rates among different gestational ages. Pharmacokinetic profile among different gestational age and body weight groups were compared by using ANOVA. RESULTS: Of the 113 subjects included, 82.3% (n = 93) achieved therapeutic concentrations at the first drug-monitoring assessment. There was no significant difference found between the percentage of term neonates who achieved therapeutic concentrations and the premature group (87.1% vs. 74.4%), p = 0.085. A total of 112 subjects (99.1%) achieved desired therapeutic trough concentration of &lt;2 mg/L. Mean gentamicin peak concentration was 8.52 mg/L (95% confidence interval [Cl], 8.13–8.90 mg/L) and trough concentration was 0.54 mg/L (95% CI, 0.48–0.60 mg/L). Mean volume of distribution, half-life, and elimination rate were 0.65 L/kg (95% CI, 0.62–0.68 L/kg), 6.96 hours (95% CI, 6.52–7.40 hours), and 0.11 hour−1 (95% CI, 0.10–0.11 hour−1), respectively. CONCLUSION: The larger percentage of subjects attaining therapeutic range with extended-interval gentamicin dosing suggests that this regimen is appropriate and can be safely used among Malaysian neonates.

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