Comparing Pharmacokinetics of Amoxicillin Given Twice or Three Times per Day to Children Older than 3 Months with Pneumonia

Abstract

Amoxicillin concentrations were determined by high-performance liquid chromatography after the first dose on days 1 and 3. After the first dose on day 1, the mean area under the concentration-time curve (AUC) for amoxicillin after the 25-mg/kg dose was 54.7 versus 24.9 g ⅐ h/ml after the 15-mg/kg dose. After the first dose on day 3, the mean AUC was 44.1 versus 28.5 g ⅐ h/ml. All but two children had plasma amoxicillin concentrations above 0.5 g/ml for >50% of the dose interval on both days. Six children on day 1 and five children on day 3 had concentrations above 1.0 g/ml for <50% of the dose interval. Acute respiratory infection (ARI) is a major cause of childhood morbidity and mortality in developing countries (3; Anonymous, Editorial, Lancet 2:699-701, 1985). Streptococcus pneumoniae and Haemophilus influenzae cause most of the bacterial infections (10, 16). The ARI control program of the World Health Organization (WHO) has developed an improved case management strategy to reduce childhood mortality from pneumonia (14, 15). Oral cotrimoxazole and amoxicillin are recommended as the antimicrobial agents of choice in the outpatient management of children with ambulatory pneumonia in developing countries. These antibiotic alternatives are especially needed for treating cases of pneumonia as outpatient therapy. Oral medication should be used whenever possible for nonhospitalized patients in order to reduce the possibility of transmission of viruses (AIDS, hepatitis) through inadequate sterilization practices (unless the use of disposable syringes can be guaranteed for all the injections) (10). The use of oral penicillin is not recommended for the treatment of childhood pneumonia because it is not effective against H. influenzae. Oral cephalosporins and new macrolides have been used with good results for the treatment of pneumonia; cost is the main reason why they are not recommended as the standard treatment of pneumonia in developing countries.Most countries have chosen oral cotrimoxazole over amoxicillin in their national ARI control programs because of its proven efficacy, lower cost, and twice-daily (b.i.d.) regimen. However, the discovery of cotrimoxazole resistance among both S. pneumoniae and H. influenzae isolates from children with ARI is cause for concern (9, 11, 13). Therefore, countries that have chosen oral cotrimoxazole are reviewing their treatment recommendations, as resistance to cotrimoxazole continues to increase.Amoxicillin is active against most S. pneumoniae and H. influenzae strains and better absorbed than ampicillin and has been widely used for treating respiratory infections (including pneumonia) in children. According to the WHO ARI guidelines, the drug should be given orally at a dosage of approximately 15 mg/kg thrice daily (t.i.d.), which may lead to compliance problems compared to oral cotrimoxazole, which should be administered b.i.d. This problem could be reduced by dosing amoxicillin b.i.d., but experience is scanty (4, 12).The objective of this study was to determine the pharmac...

Systematic review on antibiotic therapy for pneumonia in children between 2 and 59 months of age

“…Two other trials 41 42 reported amoxicillin twice a day to be a reasonable alternative to dosing three times a day. A similar finding was reported by Cook RC et al 43 in that clinical cure rate with amoxicillin/clavulanate was not different in the thrice a day versus twice a day group (difference 3.2%; 95% CI 4.36 to 10.80).…”

British Thoracic Society guidelines for the management of community acquired pneumonia in children: update 2011

“…High-dose amoxicillin twice daily is a pharmacokinetically satisfactory dosing regime and may aid compliance159 [Ib] although, in Pakistan, outcomes for infants aged 2–59 months with non-severe outpatient-treated clinical pneumonia were the same with standard and double dose amoxicillin 160. [Ib] …”

Variations in Amoxicillin Pharmacokinetic/Pharmacodynamic Parameters May Explain Treatment Failures in Acute Otitis Media

“…[12][13][14][15][16] Unfortunately, controlled crossover, dose escalation studies characterizing amoxicillin bioavailability have been performed primarily in adults and primarily across the relatively narrow dose range of 250-1000 mg. We are unaware of any published data comparing amoxicillin absorption in pediatric subjects at both the more traditional amoxicillin dose range of 13-15 mg kg and more commonly employed higher doses of 40-50 mg kg with prompt-release preparations. However, when Fonseca et al [17] evaluated amoxicillin PK in infants and children aged 5-52 months with pneumonia receiving amoxicillin 15 mg kg three times daily or amoxicillin 25 mg kg twice daily, these investigators found highly variable amoxicillin area under the plasma concentration-time curves, with a 5-to 30-fold variance observed on treatment days 1-7. In an earlier study by Barr [18] in adults, the overall variability in amoxicillin bioavailability was described to be substantial, with a range of 15-93% ( figure 1).…”