Pharmacokinetics of Rifampin in Infants and Children: Relevance to Prophylaxis Against Haemophilus influenzae Type b Disease

Pharmacokinetic studies of rifampin were performed in 38 infants and children after administration of three different oral formulations. Mean peak serum concentrations of from 9 to 11.5 µg/ml were observed one hour after a 10-mg/kg dose and the average half-life was 2.9 hours. Patients who received rifampin suspension in applesauce had smaller serum concentrations and area-under-the-curve values than did those who were given suspension alone. The mixture of rifampin powder and applesauce resulted in more variable serum levels. The concentrations of drug in tears from 18 subjects were similar to those in serum. All but one of 118 saliva specimens obtained from two to eight hours after the 10-mg/kg dose had antimicrobial activity. Of samples taken at two hours, 95% contained rifampin levels that exceeded the minimal bacterial concentration for 15 Haemophilus influenzae type b strains. Bactericidal activity against Haemophilus correlated with salivary rifampin concentrations and was detectable in virtually all specimens containing [Unknown]0.8 µg/ml. These data provide the pharmacokinetic basis for rifampin prophylaxis of close contacts of H influenzae type b disease, but are insufficient alone to recommend routine usage of rifampin for this purpose until results of additional epidemiologic studies are available.

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Comparative Pharmacokinetics of Amoxicillin and Ampicillin in Infants and Children

PEDIATRICS ◽

10.1542/peds.64.5.627 ◽

1979 ◽

Vol 64 (5) ◽

pp. 627-631 ◽

Cited By ~ 1

Author(s):

Charles M. Ginsburg ◽

George H. McCracken ◽

Marion L. Thomas ◽

Joan Clahsen

Keyword(s):

Half Life ◽

Area Under The Curve ◽

Infants And Children ◽

Peak Serum ◽

Haemophilus Influenzae Type ◽

Haemophilus Influenzae Type B ◽

Serum Concentrations ◽

Type B ◽

Group A ◽

In Infants And Children

The pharmacokinetics of amoxicillin and ampicillin were studied in 24 infants and children. Mean peak serum concentrations of 5.4 µg/ml in fasting and 3.2 µg/ml in nonfasting patients were observed after 15 mg/kg amoxicillin doses. Area under the curve values and serum half-life values were similar in fasting and nonfasting patients. The pharmacokinetics of amoxicillin (15 mg/kg) were compared to those of ampicillin (25 mg/kg). Peak serum concentrations, area under the curve values and half-life times were comparable for the two drugs. Amoxicillin (25 mg/kg) and ampicillin (25 mg/kg) were compared in cross-over fashion in 11 children. Serum concentrations of amoxicillin were consistently larger than those of ampicillin; the differences were of borderline significance at one and two hours and statistically significant at four and six hours after the dosage. The bioavailability of amoxicillin was twice that of ampicillin. Amoxicillin was detected in approximately half of the saliva samples studied. Although the salivary concentrations in many children exceeded the inhibitory level for most pneumococci and group A streptococci and for many non-β lactamase-producing Haemophilus influenzae type b strains, the clinical relevance of these observations is unknown.

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Interchangeability of Haemophilus influenzae Type b vaccines in the Primary Series: Evaluation of a Two-dose Mixed Regimen

PEDIATRICS ◽

10.1542/peds.98.5.898 ◽

1996 ◽

Vol 98 (5) ◽

pp. 898-904 ◽

Cited By ~ 1

Author(s):

Kathleen M. Bewley ◽

Joel G. Schwab ◽

Gerard A. Ballanco ◽

Robert S. Daum

Keyword(s):

Haemophilus Influenzae ◽

Randomized Clinical Trials ◽

Geometric Mean ◽

Serum Antibody ◽

Area Under The Curve ◽

Haemophilus Influenzae Type ◽

Antibody Concentration ◽

Haemophilus Influenzae Type B ◽

Type B ◽

Series Evaluation

Objective. To evaluate two- or threedose "mixed" regimens of Haemophilus influenzae type b conjugate vaccines in the priming series. Design. Two randomized clinical trials with 140 and 181 infants, respectively. Setting. Private practices in New Orleans and Chicago. Methods. In trial I, infants received one of four regimens. Two were recommended regimens for polyribosylribitol phosphate (PRP)—meningococcal protein conjugate (M) and PRP—tetanus toxoid conjugate (T). Two mixed regimens consisted of M at 2 months followed by two doses of T or PRP—diphtheria toxoid conjugate (D) at 4 and 6 months. Trial II consisted of three groups. Two were recommended regimens for M and T. The third was a two-dose mixed regimen consisting of M at 2 months and T at 4 months. Parents were interviewed and instructed to record side effects after each vaccination. Serum was assayed for H influenzae type b anticapsular antibody (anti-PRP). Results. Minor differences in safety profiles likely reflected α error. In trial I, M (lot 0884T, one of several known to have had decreased immunogenicity), probably primed for substantial increase in serum antibody when D or T was given at 4 and 6 months. In trial II, infants who received the two-dose mixed regimen (M from immunogenic lot 0116W at 2 months and T at 4 months) had a significantly higher mean area under the curve than recipients of the three-dose TIT regimen when antibody concentration was plotted against age, although the geometric mean anti-PRP antibody concentration for the MT-recipients was significantly lower at 7 months. Conclusions. M used in trial I may have primed infants despite poor immunogenicity. The two-dose mixed regimen (MT-) in trial II produced a mean anti-PRP antibody concentration with higher sustained anti-PRP concentrations from 2 to 7 months, as judged by the area under the curve, but a lower mean anti-PRP antibody concentration at 7 months.

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