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.

Serum 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 A Streptococcus 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.

Urticaria recurrente asociada a infección por Streptococcus pyogenes / Recurrent urticaria associated with group Streptococcus pyogenes infection

La mayoría de las urticarias crónicas o agudas recidivantes son idiopáticas. Presentamos un caso de urticaria aguda recidivante en una niña de tres años, en la que, tras el estudio realizado, solo se objetivó un valor elevado de anticuerpos antiestreptolisina O (ASLO). La desaparición de la urticaria tras el tratamiento con penicilina G-benzatina intramuscular, junto con la normalización de los ASLO, sugiere que la etiología de esta podría ser las infecciones recurrentes por el Streptococcus pyogenes. Destacar la importancia de incluir en el protocolo diagnóstico de la urticaria la determinación de los ASLO, lo cual permite el diagnóstico y tratamiento precoces de las infecciones por S. pyogenes (AU)

We present a case of relapsing acute urticaria in a three years old girl who after the study only showed a high value of ASLO (antistreptolysin O titer). The disappearance of urticaria after intramuscular penicillin G benzathine treatment, together with the ASLO normalization, suggested that the etiology of this could be recurrent Streptococcal infections. We conclude the importance of including ASLO determination in the diagnostic protocol of urticaria, allowing early diagnosis and treatment of Group A Streptococcus infections (AU)

Treatment of latent syphilis in HIV-infected patients with 10 d of benzylpenicillin G benethamine: a prospective study in Maputo, Mozambique.

Neurosyphilis has been reported in HIV-infected patients previously treated with penicillin G benzathine, which does not achieve treponemicidal levels in cerebrospinal fluid. Therapy combining benzylpenicillin G and its repository form benzylpenicillin G benethamine could be a potentially effective alternative enhanced regimen for treating latent syphilis in HIV-infected patients because peak serum and cerebrospinal fluid concentrations would be achieved early post-administration by the former molecule and sustained for 24 h due to the prolonged half-life of the latter. In this study, 23 asymptomatic HIV and Treponema pallidum co-infected patients received 10 d of combined therapy (2 M IU intramuscular once daily) and were followed up at 3, 6 and 12 months. None experienced side effects or clinical symptoms. Of the 18 patients who were evaluated 1 y later, 8 (44.4%) exhibited serological treatment failure, defined as a positive serum rapid plasma reagin test. In conclusion, a 10-d regimen combining penicillin G and penicillin G benethamine seems to be of no benefit compared to currently recommended treatment.

Serum concentration of penicillin in the horse after repeated intramuscular injections of procaine penicillin G alone or in combination with benzathine penicillin and/or phenylbutazone.

Twenty-one adult horses were randomly assigned into 7 groups of 3 and were treated for 5 days with procaine penicillin G, benzathine penicillin , or phenylbutazone in various combinations and dosage schedules. Serum concentration of penicillin was measured serially over a 7-day period. The highest mean peak serum concentration was 2.06 micrograms/ml. Comparable peak values were seen 2 to 4 hours after administration of 22,000 IU of procaine penicillin G/kg of body weight given once or twice daily. A minimum serum concentration of 0.25 micrograms/ml was selected as adequate for efficacy against organisms that can be considered sensitive to penicillin. Once daily administration of procaine penicillin G and, although peak concentrations were lower, some regimens of procaine and benzathine penicillin G did maintain this concentration. Concurrent phenylbutazone administration did not affect serum concentration of penicillin appreciably.

Penicillin concentrations in blood and spinal fluid after a single intramuscular injection of penicillin G benzathine.

The concentration of penicillin in cerebrospinal fluid and blood was measured after a single i.m. injection of 1.44 g penicillin G benzathine in 18 individuals (4 with neurosyphilis and 14 with neurological symptoms but not syphilis). Only one person had a treponemicidal concentration in the cerebrospinal fluid.

Comparative pharmacological evaluation of oral benzathine penicillin G and phenoxymethyl penicillin potassium in children.

Serum penicillin concentrations and urine excretion rates of oral benzathine penicillin G and phenoxymethyl penicillin potassium were evaluated in children. Mean peak serum concentration of 0.134 microgram/ml of benzathine penicillin G and 1.018 microgram/ml of phenoxymethyl penicillin potassium were measured at 125 and 35 min. The mean half-life times were 1.36 and 0.74 hr, and for area under the curve, the values were 0.34 and 1.68 microgram . hr/ml for benzathine penicillin G and phenoxymethyl penicillin potassium groups, respectively. Phenoxymethyl penicillin potassium had more reliable pharmacokinetic properties and would be the preferred forms of oral penicillin. However, all patients receiving penicillin G had penicillinemia, which was enough to inhibit most strains of Streptococcus pyogenes for a longer period than phenoxymethyl penicillin potassium. Palatability of phenoxymethyl penicillin is less than for benzathine penicillin G; the latter may be used for children in whom compliance may be a problem.

Absorption of penicillin V from mixture formulations. Comparison of potassium and benzathine salts.

The absorption rate and serum level curves of two commercial phenoxymethylpenicillin mixture preparations were compared in adult volunteers. Both the potassium salt (Primcillin) and the benzathine salt (V-Pen ped forte) of V-penicillin were rapidly absorbed and the mean peak serum levels were obtained with both preparations within the first hour after single dose administration. The mean peak level obtained with the potassium salt was several-fold higher (p less than 0.001) and was also reached within a shorter time than that of the benzathine preparation. These results confirm the earlier evidence, obtained with other formulae, for the superior bioavailability of the potassium salt of V-penicillin as compared to most other derivatives used in V-penicillin mixtures.

In vitro and in vivo evaluation of benzamidomethyl-benzylpenicillinate (FI7303). A new 'repository' form.

A new type of hydrolyzable ester of penicillin G, benzamidomethyl benzylpenicillinate (FI 7303), was studied for the antibacterial activity and kinetics of absorption in comparison with DBED-penicillin G. FI 7303 resulted to be a good repository form of penicillin G, slowly eliminated in mouse, dog and man. It exerted a remarkable therapeutic activity in mice infected with Staphylococcus aureus even when administered 26 h before infection. The protective effect in mice was more prolonged than that of DBED-penicillin G, in agreement with the longer persistence of significant blood levels.

[Depoteffect of benzathine-penicillin (author's transl)]. / Untersuchungen über die Depotwirkung von Benzathin-Penicillin

15 test persons received an injection of 2,400,000 units of benzathine penicillin. Serum levels were subsequently assayed, as well as the excretion of the antibiotic in the urine. The samples were stored in liquid-nitrogen between collection and examination. Each of the speciemens was tested 5 to 10 times and the results were ascertained by empirical evaluation of every single analysis. This assay showed the existence of mean levels above 0.036 I.U./ml in the serum and above 19.75 I.U./ml in the urine for the duration of 26 days. The evaluation of serum levels after the administration of antibiotics is difficult due to several sources of error. Reliable results can, therefore, be obtained only by examination at special institutes which possess experienced technical personnel. The establishment of reference laboratories for this purpose is suggested. The results of the study confirm the efficacy of one-shot treatment of the syphilis by administration of 2,400,000 to units of benzathine penicillin.

The bioavailability of oral penicillin V. A comparative study of the absorption of different salts of penicillin V in children.

Different salts of penicillin V (pc-V): potassium pc-V (Calciopen and Kåvepenin), calcium pc-V (Penicals) and benzathine pc-V (Meropenin) were given to 37 children (age 2 months to 4 years) with upper respiratory infections. The gastro-intestinal absorption of the drug given in a mixture was followed for three hours after administration by determination of the serum levels from capillary samples. Administration of the mixtures containing the potassium pc-V resulted in a more rapid absorption and in significantly higher plasma concentrations at 30 min than did administration of the preparations containing the calcium and benzathine salts. In four children with coeliac disease, verified by intestinal biopsy, the absorption of potassium pc-V (Calciopen) was compared with that of calcium pc-V (Penicals). A decreased absorption was found and this was most pronounced when the calcium salt was given.