scholarly journals A Population Pharmacokinetic Modeling Approach Shows that Serum Penicillin G Concentrations Are Below Inhibitory Concentrations by Two Weeks after Benzathine Penicillin G Injection in the Majority of Young Adults

2014 ◽  
Vol 58 (11) ◽  
pp. 6735-6741 ◽  
Author(s):  
Michael Neely ◽  
Edward L. Kaplan ◽  
Jeffrey L. Blumer ◽  
Dennis J. Faix ◽  
Michael P. Broderick
Keyword(s):  
Young Adults ◽  
Central Compartment ◽  
Penicillin G ◽  
Simulated Patients ◽  
Peripheral Compartment ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Data ◽  
Benzathine Penicillin ◽  
Final Population ◽  
Benzathine Penicillin G

ABSTRACTSerum penicillin G falls to low levels 2 weeks after injection as benzathine penicillin G (BPG) in young adults. Using Pmetrics and previously reported penicillin G pharmacokinetic data after 1.2 million units were given as BPG to 329 male military recruits, here we develop the first reported population pharmacokinetic model of penicillin G after BPG injection. We simulated time-concentration profiles over a broad range of pediatric and adult weights after alternative doses and dose frequencies to predict the probability of maintaining serum penicillin G concentrations of >0.02 mg/liter, a proposed protective threshold against group AStreptococcus pyogenes(GAS). The final population model included linear absorption into a central compartment, distribution to and from a peripheral compartment, and linear elimination from the central compartment, with allometrically scaled volumes and rate constants. With 1.2 million units of BPG given intramuscularly every 4 weeks in four total doses, only 23.2% of 5,000 simulated patients maintained serum penicillin G trough concentrations of >0.02 mg/liter 4 weeks after the last dose. When the doses were 1.8 million units and 2.4 million units, the percentages were 30.2% and 40.7%, respectively. With repeated dosing of 1.2 million units every 3 weeks and every 2 weeks for 4 doses, the percentages of simulated patients with a penicillin G trough concentration of >0.02 mg/liter were 37.8% and 65.2%, respectively. Our simulations support recommendations for more frequent rather than higher BPG doses to prevent recurrent rheumatic heart disease in areas of high GAS prevalence or during outbreaks.

Subcutaneous administration of benzathine benzylpenicillin G has favourable pharmacokinetic characteristics for the prevention of rheumatic heart disease compared with intramuscular injection: a randomized, crossover, population pharmacokinetic study in healthy adult volunteers

2020 ◽  
Vol 75 (10) ◽  
pp. 2951-2959
Author(s):  
Joseph H Kado ◽  
Sam Salman ◽  
Robert Henderson ◽  
Robert Hand ◽  
Rosemary Wyber ◽  
...  
Keyword(s):  
Heart Disease ◽  
Rheumatic Heart Disease ◽  
Subcutaneous Administration ◽  
Penicillin G ◽  
Population Pharmacokinetic ◽  
High Dose ◽  
Benzathine Penicillin ◽  
Pain Scores ◽  
Benzathine Penicillin G ◽  
Rheumatic Heart

Abstract Background Benzathine penicillin G has been used as monthly deep intramuscular (IM) injections since the 1950s for secondary prevention of acute rheumatic fever and rheumatic heart disease (RHD). Injection frequency and pain are major programmatic barriers for adherence, prompting calls for development of better long-acting penicillin preparations to prevent RHD. We hypothesized that subcutaneous (SC) administration of benzathine penicillin G could delay penicillin absorption when compared with IM injections. Methods To compare the pharmacokinetic profile and tolerability of benzathine penicillin G according to different routes of administration, 15 healthy males participated in a randomized crossover study to receive benzathine penicillin G by either SC or IM routes, with a 10 week washout period before the second dose by the alternative route. Ultrasound guidance confirmed injection location. Penicillin concentrations and pain scores were measured for 6 weeks following injections. Results SC administration was well tolerated with no significant differences in pain scores. Following SC injection, the principal absorption half-life (95% CI) was 20.1 (16.3–29.5) days and 89.6% (87.1%–92.0%) of the drug was directed via this pathway compared with 10.2 (8.6–12.5) days and 71.3% (64.9%–77.4%) following IM administration. Lower peak and higher trough penicillin concentrations resulted following SC injection. Simulations demonstrated that SC infusion of higher doses of benzathine penicillin G could provide therapeutic penicillin concentrations for 3 months. Conclusions SC administration of benzathine penicillin G is safe and significantly delays penicillin absorption. High-dose benzathine penicillin G via the SC route would fulfil many product characteristics required for the next generation of longer-acting penicillins for use in RHD.

scholarly journals Pharmacokinetics of piperacillin in critically ill Australian Indigenous patients with severe sepsis

2016 ◽  
pp. AAC.01657-16 ◽  
Author(s):  
Danny Tsai ◽  
Penelope Stewart ◽  
Rajendra Goud ◽  
Stephen Gourley ◽  
Saliya Hewagama ◽  
...  
Keyword(s):  
Severe Sepsis ◽  
Critically Ill ◽  
Total Body Weight ◽  
Compartment Model ◽  
Central Compartment ◽  
Volume Of Distribution ◽  
Peripheral Compartment ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Data ◽  
Population Pharmacokinetic Study

Objectives: There are no available pharmacokinetic data to guide piperacillin dosing in critically ill Australian Indigenous patients despite numerous reported physiological differences. This study aimed to describe the population pharmacokinetics of piperacillin in critically ill Australian Indigenous patients with severe sepsis.Methods: A population pharmacokinetic study of Indigenous patients with severe sepsis was conducted in a remote hospital intensive care unit. Plasma samples were collected over two dosing intervals and assayed by validated chromatography. Population pharmacokinetic modelling was conducted using Pmetrics®.Results: Nine patients were recruited and a two compartment model adequately described the data. Piperacillin clearance (CL), volume of distribution of the central compartment (Vc), distribution rate constant from central to peripheral compartment and from peripheral to central compartment were 5.6 ± 3.2 L/h, 14.5 ± 6.6 L, 1.5 ± 0.4 h-1and 1.8 ± 0.9 h-1respectively, where CL and Vcwere found to be described by creatinine clearance (CrCL) and total body weight respectively.Conclusion: In this patient population, piperacillin demonstrated high interindividual pharmacokinetic variability. CrCL were found to be the most important determinant of piperacillin pharmacokinetics.

scholarly journals Benzathine Penicillin G in the Control of Gonorrhoea

1957 ◽  
Vol 33 (1) ◽  
pp. 40-42
Author(s):  
C. E. Hookings ◽  
L. M. Graves
Keyword(s):  
Penicillin G ◽  
Benzathine Penicillin ◽  
Benzathine Penicillin G

Three-Versus Four-week Administration of Benzathine Penicillin G: Effects on Incidence of Streptococcal Infections and Recurrences of Rheumatic Fever

PEDIATRICS ◽  
1996 ◽  
Vol 97 (6) ◽  
pp. 984-988
Author(s):  
Hung-Chi Lue ◽  
Mei-Hwan Wu ◽  
Jou-Kou Wang ◽  
Fen-Fen Wu ◽  
Yu-Nian Wu
Keyword(s):  
Rheumatic Fever ◽  
Color Doppler ◽  
Clinic Visit ◽  
Penicillin G ◽  
Controlled Study ◽  
Streptococcal Infections ◽  
Benzathine Penicillin ◽  
Acute Phase Reactants ◽  
Weight Percentage ◽  
Benzathine Penicillin G

Objective. To investigate the effects of 3-week versus 4-week administration of benzathine penicillin G (BPG) on the incidence of Group A streptococcal infections and the recurrences of rheumatic fever (RF). Study Design. We started, in 1979, randomly allocating all patients with RF to a 3-week or 4-week BPG prophylaxis program. They were examined at the RF clinic, every 3 to 6 months, and at any time they did not feel well. During 1979 to 1989, throat cultures and sera for antistreptolysin O and streptozyme titers were obtained at each clinic visit. Chest radiographs, electrocardiogram, color Doppler echocardiograms, and acute phase reactants were obtained. Subjects. Two hundred forty-nine patients fulfilled the revised Jones criteria and were followed until December 1991: 124 in the 3-week and 125 in the 4-week program. Their age, sex, weight, percentage with history of RF, severity of cardiac involvement, follow-up duration, and compliance to program were comparable. Eight hundred eighty throat cultures were collected in the 3-week program and 770 were collected in the 4-week program. Six hundred sixteen and 627 sera were determined in each program for antistreptolysin O, and 582 and 592 sera for streptozyme titers. Results. True streptococcal infections occurred in both programs: 39 infections in the 3-week program, and 59 infections in the 4-week program (7.5 vs 12.7 per 100 patient-years). Four infections with no antibody response occurred in the 3-week program, and three such infections in the 4-week program. Nine RF recurrences occurred in 8 patients in the 3-week program, and 16 recurrences in 16 patients in the 4-week program. Prophylaxis failure occurred in 2 of 124 patients in the 3-week program, and in 10 of 125 patients in the 4-week program (0.25 vs 1.29 per 100 patient-years). The overall recurrences/infections rate in each program was comparable, 13.6% vs 15.5%, but the recurrences/infections rate due to prophylaxis failure was higher in the 4-week program than in the 3-week program, 3.0% versus 9.7%. Conclusions. This 12-year prospective and controlled study documented that streptococcal infections and RF recurrences occurred more often in the 4-week program than in the 3-week program. The risk of prophylaxis failure was fivefold greater in the 4-week program than in the 3-week program.

Rheumatic Fever Article Questioned

PEDIATRICS ◽  
1984 ◽  
Vol 74 (6) ◽  
pp. 1133-1134
Author(s):  
SYLVIA P. GRIFFITHS
Keyword(s):  
Rheumatic Fever ◽  
Intramuscular Injection ◽  
Group A Streptococcus ◽  
Penicillin G ◽  
Benzathine Penicillin ◽  
Benzathine Penicillin G ◽  
Group A

To the Editor.— The suggestion of Nordin1 that there may be a need to re-evaluate the current recommended prophylaxis for children with rheumatic fever is valid, particularly if carefully planned and controlled studies could be carried out. However, the author's contention that "It has been assumed that the levels of penicillin [following monthly intramuscular injection of 1.2 million units of benzathine penicillin G] are adequate to prevent reinfection with group A streptococcus, and hence to prevent recurrences of rheumatic fever" has always been qualified by others.

scholarly journals Real Life Population Pharmacokinetics Modelling of Eight Factors VIII in Patients with Severe Haemophilia A: Is It Always Relevant to Switch to an Extended Half-Life?

Pharmaceutics ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 380 ◽  
Author(s):  
Quentin Allard ◽  
Zoubir Djerada ◽  
Claire Pouplard ◽  
Yohann Repessé ◽  
Dominique Desprez ◽  
...  
Keyword(s):  
Half Life ◽  
Random Effect ◽  
Real Life ◽  
Compartment Model ◽  
Central Compartment ◽  
Peripheral Compartment ◽  
Population Pharmacokinetic ◽  
Severe Haemophilia ◽  
Fviii Activity ◽  
Data Files

We retrospectively analysed the data files of 171 adults and 87 children/adolescents with severe haemophilia, except for 14 patients (moderate; minor) (1), to develop a global population pharmacokinetic (PK) model for eight factors VIII (FVIII) that could estimate individual PK parameters for targeting the desired level of FVIII activity (FVIII:C); and (2) to compare half-life (HL) in patients switching from a standard half-life (SHL) to an extended half-life (EHL) and evaluate the relevance of the switch. One-stage clotting assay for the measurement of FVIII activity (FVIII:C, IU/mL) was used for population PK modelling. The software, Monolix version 2019R1, was used for non-linear mixed-effects modelling. A linear two-compartment model best described FVIII:C. The estimated PK parameters (between-subject variability) were: 2640 mL (23.2%) for volume of central compartment (V1), 339 mL (46.8%) for volume of peripheral compartment (V2), 135 mL/h for Q (fixed random effect), and 204 mL/h (34.9%) for clearance (Cl). Weight, age, and categorical covariate EHL were found to influence Cl and only weight for V1. This model can be used for all of the FVIII cited in the study. Moreover, we demonstrated, in accordance with previous studies, that Elocta had longer half-life (EHL) than SHL (mean ratio: 1.48) as compared to Advate, Factane, Kogenate, Novoeight, and Refacto.

Benzathine Penicillin G in the Treatment of Neurosyphilis

1982 ◽  
Vol 16 (3) ◽  
pp. 205-210 ◽  
Author(s):  
Paul G. Cuddy
Keyword(s):  
Case Reports ◽  
Diagnosis And Treatment ◽  
Recent Case ◽  
Penicillin G ◽  
Controlled Trials ◽  
Benzathine Penicillin ◽  
Benzathine Penicillin G

The definition, pathogenesis, incidence, diagnosis, and treatment of neurosyphilis are discussed. Controlled trials of benzathine penicillin in the treatment of neurosyphilis are reviewed, as are recent case reports of benzathine penicillin failures. Although few well-controlled studies exist to document conclusively the efficacy of benzathine penicillin in the treatment of neurosyphilis, its use is recommended in selected situations.

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