Clinical trial NCT01499875: A Pharmacokinetic and Pharmacodynamic Study of Phenoxymethylpenicillin for Children
Official title: A Pharmacokinetic and Pharmacodynamic Study of Phenoxymethylpenicillin for Children
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Phenoxymethylpenicillin
Keywords: Pharmacokinetic
Pharmacodynamic
Phenoxymethylpenicillin
Children
Lead sponsor: University of Aarhus
Sponsor class: OTHER
Collaborators: name: Aarhus University Hospital Skejby
name: Department of Microbiological Surveillance and Research, SSI.
First posted: 2011-12-26
Enrollment: 80
Sex: ALL
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The aim of this trial is to evaluate the pharmacokinetics and pharmacodynamics of penicillin V in non-infectious children to estimate the optimum dosage regime in children.

Detailed description: Although occasionally questioned, the efficacy of penicillin in eradication of respiratory tract infections in children has not been convincingly reported in the literature. Two randomized multicenter antibiotic efficacy trials have been reported in eradication of group A streptococci where both oral and intramuscular administration of penicillin had relatively high microbiologic failure rates. But the trials only confirm that the treatment is not effective in the given dose. The recent recommendations on penicillin are unfortunately based upon past practices, clinical trial results and recent resistance trends and pharmacodynamics have not been considered to support the choice of drug and dosage regimen. Some pharmacodynamic trials have been made on meropenem, cefotaxime, piperacillin-tazobactam and amoxicillin in children but so fare no trials have been described on penicillin. It is well described in adults but the absorption and secretion might be depended on age. Penicillin exhibit a time-dependent killing which means that the time over minimal inhibitory concentration (MIC) is the parameter best related to efficacy.

Methods:

The investigators evaluate the pharmacokinetics and pharmacodynamics of penicillin V in non-infectious Danish children at age 0-10 years who were admitted for a chromium-51-EDTA-clearance test. The investigators excluded children with allergy to penicillin and children with a prior known reduced glomerular filtration rate. The parents of each child who participated gave written informed consent before the study and ethical approval was obtained.

Antimicrobial dosage and administration:

40 children were assigned to receive per oral penicillin suspension 22-32 mg/kg. The dosage was estimated 25 mg/kg by the weight the parents rapported and they had a weight control at admission. The exact given dose was then calculated. The penicillin were not taken on an empty stomach to imitate reality as much as possible and the time of administration was noted. Another 40 children were given 50 mg/kg penicillin mixture.

Samples:

Blod samples of 1 ml were taken after 0, 15, 30, 60, 90, 120 minutes after the Crom-EDTA examination had started giving a dispersion in time compared to the intake of penicillin. The samples were collected in vacuum tubes containing EDTA as an anticoagulant and then centrifuged quickly. The separated serum were placed in cryovials before frozen.

Eligibility criteria: Inclusion Criteria:

* Non-infectious Danish children at age 0-10 years who were admitted for a chromium51EDTA clearance test

Exclusion Criteria:

* Children with allergy to penicillin and children with a prior known reduced glomerular filtration rate

Primary outcomes:
measure: Phenoxymethylpenicillin concentrations
timeFrame: up to 7 hours after the penicillin is taken
Secondary outcomes:
Other outcomes:
Locations:
city: Skejby
country: Denmark
facility: Department of Pediatrics, Århus University Hospital
state: Aarhus
Study officials:
affiliation: Department of Pediatrics, Århus University Hospital, Skejby
name: Niels H Birkebæk, PhD
role: STUDY_CHAIR
References: