scholarly journals The Population Pharmacokinetics of Rifampicin in Japanese Pulmonary Tuberculosis Patients

Drug Research ◽  
2020 ◽  
Vol 70 (05) ◽  
pp. 199-205
Author(s):  
Takahiro Nishimura ◽  
Haruichi Kohno ◽  
Hideaki Nagai ◽  
Daisuke Maruoka ◽  
Yuichi Koike ◽  
...  
Keyword(s):  
Population Pharmacokinetics ◽  
Japanese Patients ◽  
Morbidity Rate ◽  
Pharmacokinetic Parameters ◽  
Population Pharmacokinetic ◽  
High Morbidity ◽  
Power Model ◽  
Time Data ◽  
Nonlinear Mixed Effects Model ◽  
High Morbidity Rate

AbstractIn Japan, tuberculosis has been recognized as one of the major infections requiring urgent measures because of its high morbidity rate even now especially in elderly people suffering from tuberculosis during the past epidemic and its reactivation. Hence, many Japanese clinicians have made efforts to suppress the onset of tuberculosis and treat it effectively. The objectives of this study are to (1) identify covariate(s) that may explain the variation of rifampicin, which is the key antitubercular agent, under the steady-state by evaluating its population pharmacokinetics and (2) to propose an appropriate dosing method of rifampicin to Japanese patients. For this purpose, serum concentration–time data were obtained from 138 patients receiving rifampicin (300–450 mg) and isoniazid (300–400 mg) every day over 14 days, and analyzed using nonlinear mixed effects model. Thereby, population pharmacokinetic parameters were estimated followed by elucidating relations between the parameters and statistical factors. The analysis adopted one-compartment model including Lag-time by assuming that the absorption process is 0+1st order. The analyses demonstrate that meal affected the bioavailability, primary absorption rate constant, and zero order absorption time in the constructed model. A body weight calculated from the power model was selected as the covariate by the Stepwise Covariate Model method and found to highly affect the clearance in the range from −31.6% to 47.4%. We conclude that the dose in Japanese tuberculous patients can be well estimated by the power model formula and should be taken into consideration when rifampicin is administered.

scholarly journals Population Pharmacokinetics of Arbekacin in Patients Infected with Methicillin-Resistant Staphylococcus aureus

2006 ◽  
Vol 50 (11) ◽  
pp. 3754-3762 ◽  
Author(s):  
Yusuke Tanigawara ◽  
Reiko Sato ◽  
Kunihiko Morita ◽  
Mitsuo Kaku ◽  
Naoki Aikawa ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Population Pharmacokinetics ◽  
Elderly Subjects ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Peripheral Compartment ◽  
Population Pharmacokinetic ◽  
Time Data ◽  
Mixed Effect ◽  
Methicillin Resistant

ABSTRACT Arbekacin, a derivative of dibekacin, is an aminoglycoside developed and widely used in Japan for the treatment of patients infected with methicillin-resistant Staphylococcus aureus (MRSA). The population pharmacokinetics of arbekacin was investigated in the Japanese, using 353 patients infected with MRSA and 50 healthy or renally impaired volunteers. The age of the study population ranged from 8 to 95 years, and weight ranged from 10.8 to 107 kg. In total, 1,581 serum arbekacin concentrations were measured (primarily from routine patient care) and used to perform the present pharmacokinetic analysis. Drug concentration-time data were well described by a two-compartment open model. Factors influencing arbekacin pharmacokinetics were investigated using a nonlinear mixed-effect model analysis. The best-developed model showed that drug clearance (CL) was related to creatinine clearance (CLCR), age, and body weight (WT), as expressed by CL (liter/h) = 0.0319CLCR + (26.5/age) (CLCR < 80 ml/min) and CL (liter/h) = 0.0130 CLCR + 0.0342WT + (26.5/age) (CLCR ≥ 80 ml/min). The volume of distribution for the central and peripheral compartments was different in healthy subjects and infected patients, and this difference was more pronounced among disease types. The elderly subjects (aged 80 years or over) exhibited, on average, a 19% greater volume for the central compartment. The volumes for the peripheral compartment were 50.6 liters in patients with pneumonia and 24.3 liters in patients with sepsis. The population pharmacokinetic parameters of arbekacin obtained here are useful for optimal use of this aminoglycoside in the treatment of MRSA-infected patients.

scholarly journals Population Pharmacokinetic and Pharmacodynamic Target Attainment Analysis of Cefazolin in the Serum and Hip Joint Capsule of Patients Undergoing Total Hip Arthroplasty

2021 ◽  
Author(s):  
Toshiaki Komatsu ◽  
Yui Natsume ◽  
Katsufumi Uchiyama ◽  
Shinsuke Ikeda ◽  
Yoshinori Tomoda ◽  
...  
Keyword(s):  
Total Hip Arthroplasty ◽  
Population Pharmacokinetics ◽  
Hip Joint ◽  
Hip Arthroplasty ◽  
Joint Capsule ◽  
Pharmacokinetic Parameters ◽  
Population Pharmacokinetic ◽  
Serum Samples ◽  
Nonlinear Mixed Effects Model ◽  
Total Hip

The objectives of this study were to evaluate the population pharmacokinetics of prophylactic cefazolin (CFZ) from its serum and hip joint capsule concentrations in patients undergoing total hip arthroplasty, and to establish pharmacodynamic target concentration exceeding the MIC for designing an effective dosing regimen for serum and the hip joint capsule. We analyzed 249 serum samples and 125 hip joint capsule samples from 125 individuals using a nonlinear mixed-effects model. The pharmacodynamic index target value obtained from our results indicates the probability of maintaining CFZ trough and hip joint capsule concentrations exceeding the MIC of 1 mg/L, to account for methicillin-susceptible S. aureus (MSSA). We estimated the population pharmacokinetics using a two-compartment model. The estimated population pharmacokinetic parameters were as follows: CL (L/h) = 1.46 × (CLcr (mL/min)/77)0.891, Vc (L) = 7.5, Q (L/h) = 3.38, and VJC (L) = 36.1. The probability of achieving concentrations exceeding the MIC90 for MSSA was approximately 100% for serum and 100% for the hip joint capsule at 3 h after the initial dose. Our findings suggest that population-based parameters are useful for evaluating CFZ pharmacokinetics and that individual dosages should be determined based on the dosage regimen that achieves and maintains adequate tissue CFZ concentration.

POPULATION PHARMACOKINETICS AND DOSING OPTIMIZATION OF TEICOPLANIN IN CHILDREN WITH MALIGNANT HAEMATOLOGICAL DISEASE

2015 ◽  
Vol 101 (1) ◽  
pp. e1.41-e1
Author(s):  
Wei Zhao ◽  
Daolun Zhang ◽  
Thomas Storme ◽  
André Baruchel ◽  
Xavier Declèves ◽  
...  
Keyword(s):  
Population Pharmacokinetics ◽  
Haematological Malignancy ◽  
External Validation ◽  
Predictive Performance ◽  
Paediatric Population ◽  
Pharmacokinetic Parameters ◽  
Therapeutic Drug ◽  
Population Pharmacokinetic ◽  
High Risk Population ◽  
Dosing Regimen

BackgroundChildren with haematological malignancy represent an identified subgroup of the paediatric population with specific pharmacokinetic parameters. In these patients, inadequate empirical antibacterial therapy may result in infection-related morbidity and increased mortality, making optimization of the dosing regimen essential. As paediatric data are limited, our aim was to evaluate the population pharmacokinetics of teicoplanin in order to define the appropriate dosing regimen in this high-risk population.MethodsThe current dose of teicoplanin was evaluated in children with haematological malignancy. Population pharmacokinetics of teicoplanin was analysed using NONMEM software. The dosing regimen was optimised based on the final model.ResultsEighty-five children (age range: 0.5 to 16.9 years) were included. Therapeutic drug monitoring and opportunistic samples (n=143) were available for analysis. With the current recommended dose of 10 mg/kg/day, 41 children (48%) had sub-therapeutic steady-state trough concentrations (Css,min<10 mg/liter). A two-compartment pharmacokinetic model with first-order elimination was developed. Systematic covariate analysis identified that bodyweight (size) and creatinine clearance significantly influenced teicoplanin clearance. The model was validated internally. Its predictive performance was further confirmed in an external validation. In order to reach the target AUC of 750 mg·h/L, 18 mg/kg was required for infants, 14 mg/kg for children and 12 mg/kg for adolescents. A patient-tailored dose regimen was further developed and reduced variability in AUC and Css,min values compared to the mg/kg-basis dose, making the modelling approach an important tool for dosing individualization.ConclusionsThis first population pharmacokinetic study of teicoplanin in children with haematological malignancy provided evidence-based support to individualize teicoplanin therapy in this vulnerable population.

Population Pharmacokinetics of Piritramide in Surgical Patients 

1999 ◽  
Vol 90 (1) ◽  
pp. 7-15 ◽  
Author(s):  
Thomas Bouillon ◽  
Daniela Kietzmann ◽  
Rudiger Port ◽  
Ingolf Meineke ◽  
Andreas Hoeft
Keyword(s):  
Population Pharmacokinetics ◽  
Venous Blood ◽  
Compartment Model ◽  
Mixed Effects ◽  
Pharmacokinetic Parameters ◽  
Effect Compartment ◽  
Bolus Administration ◽  
Time Data ◽  
Intermittent Bolus ◽  
Patient Consent

Background Piritramide is a synthetic opioid used for postoperative analgesia in several European countries. The authors present a mixed-effects model of its population pharmacokinetics in patients undergoing surgery. Methods After institutional approval and informed patient consent was obtained, 29 patients who were classified as American Society of Anesthesiologists physical status I or II and aged 21-82 yr were enrolled in the study. They received 0.2 mg/kg piritramide as an intravenous bolus before anesthesia was induced. Central venous blood samples were drawn for as long as 48 h after administration of the drug. The plasma concentration of piritramide was determined by gas chromatography. The concentration-time data were analyzed by mixed-effects modeling. Target-controlled infusions and intermittent bolus regimens were simulated to identify a regimen suitable for patient-controlled analgesia based on population pharmacokinetics and published pharmacodynamic data. Results The pharmacokinetics of piritramide were described adequately by a linear three-compartment model. Patient age and weight were significant covariates. The values of the pharmacokinetic parameters are: V1 = 50.5 [1], V2 = 150 x (1 + 9.32 x 10(-3) x (age - 47 yr)) [l], V3 = 212 x (1 + 6.37 x 10(-3) x (age - 47 yr)) [l], Cl1 = 0.56 x (1 - 6.14 x 10(-3) x (age - 47 yr)) [l/min], Cl2 = 8.25 x (1 + 2.02 x 10(-2) x (Wt - 74 kg)) [l/min], Cl3 = 0.80 [l/min]. The age of 47 yr and the weight of 74 kg refer to the median values for these factors in the patients studied. Rapid distribution, slow distribution, and elimination half-lives for the median patient are 0.05, 1.34, and 10.43 h, respectively. The context-sensitive half-time after a 24-h infusion is predicted at 10.5 h in a 75-yr-old patient compared with 7 h for the median patient. Conclusions Piritramide is distributed extensively and eliminated slowly. The pharmacokinetic profile of the drug allows for intermittent bolus administration even when constant effect compartment concentrations are desirable, e.g., for PLA.

scholarly journals Surveillance of influenza A H1N1 2009 among school children during 2009 and 2010 in São Paulo, Brazil

2012 ◽  
Vol 45 (5) ◽  
pp. 563-566 ◽  
Author(s):  
Sandra Baltazar Guatura ◽  
Aripuana Sakurada Aranha Watanabe ◽  
Clarice Neves Camargo ◽  
Ana Maria Passos ◽  
Sheila Negrini Parmezan ◽  
...  
Keyword(s):  
School Children ◽  
Influenza A ◽  
Respiratory Infections ◽  
Vaccination Campaign ◽  
Sao Paulo ◽  
Morbidity Rate ◽  
High Morbidity ◽  
São Paulo ◽  
High Morbidity Rate ◽  
Influenza A H1n1

INTRODUCTION: Influenza A H1N1 2009 is associated with a high morbidity rate among children around the world, including Brazil. This survey was conducted on samples of symptomatic children (< 12 years) to investigate the influenza virus as the etiological agent of respiratory infections in a day care school in a health facility during the first and second pandemic wave of H1N1 (2009-2010) in São Paulo, Brazil. METHODS: Influenza infections were determined by real-time PCR in 34% (47/137) of children with a median age of 5 years (8 months - 12 years), from June to October 2009 and in 16% (14/85) of those with median age of 6 years (1-12 years), from March to November 2010. RESULTS: In general, most positive cases (64%) occurred in children aged 5-12 years, this age group was significantly the most affected (39.8%, p = 0.001, OR = 8.3, CI 95% 1.9-36.9). Wheezing was reported by 31% (19/61) and dyspnea by 23% (14/61) of the studied patients. An outbreak of influenza H1N1 with an attack rate of 35.7% among children (median age 6 years) was documented in April 2010, before the vaccination campaign against the pandemic virus was extended for children up to 5 years in Brazil. CONCLUSIONS: Therefore, the study reinforces the recommendation to immunize school children to reduce the incidence of the disease.

scholarly journals Unsafe abortion among secondary school girls in a local authority in South-South Nigeria

2020 ◽  
Vol 9 (9) ◽  
pp. 3547
Author(s):  
Matthias G. Abah ◽  
Emem E. Bassey ◽  
Emmanuel B. Edu ◽  
Okupa D. Ovie
Keyword(s):  
Secondary School ◽  
Sex Education ◽  
Unwanted Pregnancy ◽  
Morbidity Rate ◽  
High Morbidity ◽  
School Students ◽  
Cross Sectional ◽  
Level Of Education ◽  
Dilation And Curettage ◽  
High Morbidity Rate

Background: Voluntary abortion for social reasons is illegal in Nigeria; however, the practice remains mostly clandestine and unsafe with varying consequences and determinants yet to be studied in all settings.Methods: A descriptive cross-sectional study design was used to assess the prevalence, practice and determinants of termination of pregnancy amongst 119 female Secondary School students in South-South Nigeria.Results: The prevalence of abortion was 57.1%. Most of the students were above 18years (58.8%), Christian (95.8%) and of rural residence (66.4%). While 58.8% had experienced an unwanted pregnancy, 61.4% had used some form of contraceptive with condom being the commonest (39.5%). Most (89.1%) have heard of abortions while 67.6% and 16.2% have had abortions once and twice respectively with the top reasons for abortion being that they were still in school (33.8%), too young (25.9%) and to avoid shame or stigma associated with the pregnancy (11.7%). Dilation and curettage was the predominant method employed (40.2%) mainly by medical doctors (34.1% and pharmacists (35.6%) while 51 (75%) had post-abortal complaints such as pain (41.2%) and bleeding (21.6%). There was a significant association between having an abortion and place of residence (rural more than urban), (p=0.04), being pregnant more than once (p<0.001), mothers` level of education (p=0.03), fathers` level of education (p=0.02) and mothers occupation (p=0.04).Conclusions: The prevalence of abortion is high and complicated by high morbidity rate despite a higher contraceptive prevalence rate whose major determinants were the socio-demographic characteristics of the parents. There is a need for early sex education from parents as this can influence abortion perception and practice in later years.

scholarly journals Monoclonal Antibodies in Multiple Sclerosis: Present and Future

Biomedicines ◽  
2019 ◽  
Vol 7 (1) ◽  
pp. 20 ◽  
Author(s):  
Natalia Voge ◽  
Enrique Alvarez
Keyword(s):  
Multiple Sclerosis ◽  
Monoclonal Antibodies ◽  
Morbidity Rate ◽  
High Morbidity ◽  
Disease Modifying Therapies ◽  
High Morbidity Rate ◽  
New Treatments ◽  
Near Future ◽  
Risk Ratios

The global incidence of multiple sclerosis (MS) appears to be increasing. Although it may not be associated with a high mortality rate, this disease has a high morbidity rate which affects the quality of life of patients and reduces their ability to do their activities of daily living. Thankfully, the development of novel disease modifying therapies continues to increase. Monoclonal antibodies (MABs) have become a mainstay of MS treatment and they are likely to continue to be developed for the treatment of this disease. Specifically, MABs have proven to be some of the most efficacious treatments at reducing relapses and the inflammation in MS patients, including the first treatment for primary progressive MS and are being explored as reparative/remyelinating agents as well. These relatively new treatments will be reviewed here to help evaluate their efficacy, adverse events, immunogenicity, and benefit-risk ratios in the treatment of the diverse spectrum of MS. The focus will be on MABs that are currently approved or may be approved in the near future.

scholarly journals Population Pharmacokinetics of Rifapentine and Its Primary Desacetyl Metabolite in South African Tuberculosis Patients

2005 ◽  
Vol 49 (11) ◽  
pp. 4429-4436 ◽  
Author(s):  
Grant Langdon ◽  
Justin Wilkins ◽  
Lynn McFadyen ◽  
Helen McIlleron ◽  
Peter Smith ◽  
...  
Keyword(s):  
Population Pharmacokinetics ◽  
South African ◽  
Parent Drug ◽  
Tuberculosis Patient ◽  
Pharmacokinetic Parameters ◽  
Oral Clearance ◽  
Time Data ◽  
Primary Metabolite ◽  
Mixed Effect ◽  
Tuberculosis Patients

ABSTRACT This study was designed to describe the population pharmacokinetics of rifapentine (RFP) and 25-desacetyl RFP in a South African pulmonary tuberculosis patient population. Special reference was made to studying the influence of previous exposure to rifampin (RIF) and the variability in pharmacokinetic parameters between patients and between occasions and the influence of different covariates. Patients were included in the study if they had been receiving first-line antimycobacterial therapy (rifampin, isoniazid, pyrazinamide, and ethambutol) for not less than 4 weeks and not more than 6 weeks and were divided into three RFP dosage groups based on weight: 600 mg, <45 kg; 750 mg, 46 to 55 kg; and 900 mg, >55 kg. Participants received a single oral dose of RFP together with concomitant antimycobacterial agents, excluding RIF, on study days 1 and 5 after they ingested a soup-based meal. The RFP and 25-desacetyl RFP concentration-time data were analyzed by nonlinear mixed-effect modeling using NONMEM. The pharmacokinetics of the parent drug were modeled separately, and the individual pharmacokinetic parameters were used as inputs for the 25-desacetyl RFP pharmacokinetic model. A one-compartment disposition model was found to best describe the data for both the parent and the metabolite, and the metabolite was assumed to be formed only from the central compartment of the parent drug. Prior treatment with RIF did not alter the pharmacokinetics of RFP but appeared to increase the excretion of 25-desacetyl RFP in a nonlinear fashion. The RFP oral clearance and volume of distribution were found to increase by 0.049 liter/h and 0.691 liter, respectively, with a 1-kg increase from the median weight of 50 kg. The oral clearance of 25-desacetyl RFP was found to be 35% lower in female patients. The model developed here describes the population pharmacokinetics of RFP and its primary metabolite in tuberculosis patients and includes the effects of prior administration with RIF and covariate factors.

High morbidity rate after converted laparoscopic colorectal surgery

1995 ◽  
Vol 82 (10) ◽  
pp. 1406-1408 ◽  
Author(s):  
K. Slim ◽  
D. Pezet ◽  
Y. Riff ◽  
E. Clark ◽  
J. Chipponi
Keyword(s):  
Colorectal Surgery ◽  
Laparoscopic Colorectal Surgery ◽  
Morbidity Rate ◽  
High Morbidity ◽  
High Morbidity Rate

scholarly journals Analysis Of Heart Decrease In Hypertension Patients With Karotis Artery Massage

2017 ◽  
Vol 1 (2) ◽  
pp. 1-5
Author(s):  
Asnidar ◽  
Tenriwati
Keyword(s):  
Public Health ◽  
Heart Rate ◽  
Carotid Artery ◽  
Health Center ◽  
Sampling Technique ◽  
Morbidity Rate ◽  
High Heart Rate ◽  
High Morbidity ◽  
Public Health Center ◽  
High Morbidity Rate

Hypertension is a disease that causes a high morbidity rate. The purpose of this study was to analyze the decrease in heart rate of hypertensive patients before and after doing massage on the carotid artery at the Bontobangun Public Health Center. design with population and sample that is all hypertension patients in Public Health Center of Bonto Public Health Center as many as 30 people. The sampling technique used was accidentaly sampling. The results of this study were in the pre-test there were 17 people (56.7%) who were in the category of moderate heart rate, 13 people (43.3%) high heart rate, in the post-test there were 25 people (83.3%) who had moderate heart rate , and 5 people (16.7%) had high heart rates. The conclusion of this study is that there is a decrease in heart rate of hypertension patients after carotid artery massage in public polyclinic public clinics at Bonto Wake with a value of p = 0.008 <α = 0.05. suggestions from this study are so that the results of this study can add a reference regarding carotid artery massage to decrease heart rate in patients with hypertension in the general poly bontobangun puskesmas.

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