Clinical Pharmacokinetics in Infants and Children A Reappraisal

Kearns, Gregory L.; Reed, Michael D.

doi:10.2165/00003088-198900171-00005

Cited by 174 publications

(84 citation statements)

References 255 publications

(238 reference statements)

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“…2). This pattern of increasing elimination rate with increasing age has been observed with other penicillin and cephalosporin analogs (19,26,32,35). Comparison of the pharmacokinetic data derived for the older infants and children in our study with data obtained from healthy adult volunteers (16,18,33) reveals very similar disposition characteristics.…”

Section: Resultssupporting

confidence: 80%

Single-dose pharmacokinetics of piperacillin and tazobactam in infants and children

Reed

Goldfarb

Yamashita

et al. 1994

Antimicrob Agents Chemother

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The pharmacokinetics of piperacillin and tazobactam were assessed after single-dose administration to 47 infants and children. Study subjects ranging in age from 2 months to 12 years were randomized to receive one of two different doses of a piperacillin-tazobactam combination (8:1): a low dose (n = 23) of 50 and 6.25 mg of piperacillin and tazobactam per kg of body weight, respectively, or a high dose (n = 24) of 100 and 12.5 mg, respectively. The pharmacokinetic behavior of tazobactam was very similar to that observed for piperacillin, supporting the use of these two agents in a fixed-dose combination. No differences in the pharmacokinetics of piperacillin or tazobactam were observed between the two doses administered. The elimination parameters half-life and total body clearance decreased and increased, respectively, with increasing age, whereas volume parameters (volume of distribution and steady-state volume of distribution) remained relatively constant for both compounds. The primary metabolite of tazobactam, metabolite Ml, was measurable in the plasma of 18 of the 47 study subjects; 17 of these 18 subjects received the high doses. More than 70%o of the administered piperacillin and tazobactam doses were excreted unchanged in the urine over a 6-h collection period. These data combined with the known in vitro susceptibilities of a broad range of pediatric bacterial pathogens indicate that a dose of 100 mg of piperacillin and 12.5 of mg tazobactam per kg of body weight administered as a fixed-dose combination every 6 to 8 h would be appropriate to initiate clinical efficacy studies in infants and children for the treatment of systemic infections arising outside of the central nervous system. The beta-lactam antibiotics are among the most widely prescribed classes of drugs for infants and children. For decades these drugs have been used successfully for the treatment of most bacterial infections arising in childhood, particularly for those infections involving skin and soft tissues, the genitourinary tract, the upper and lower respiratory tracts, and the central nervous system (30,31). Unfortunately, over the last decade, the number of infections caused by penicillinand cephalosporin-resistant bacteria has increased dramatically, reducing the clinical utilities of these safe and previously very effective antibiotics (22,29). By 1975 nearly 85% of all isolates of Staphylococcus aureus were resistant to penicillin (22), and a similar trend has been observed for Haemophilus influenzae and Moraxella catarrhalis, in which nearly 40% of all H. influenzae type B strains and more than 80% of M. catarrhalis isolates are resistant to ampicillin (6, 29). Moreover, variable and changing susceptibility patterns to a wide range of penicillin and cephalosporin antibiotics are observed for other gram-negative pathogens (6,22,29).Bacterial resistance to beta-lactam antibiotics is most often mediated via one of three primary mechanisms; alterations in drug binding to their cellular targets, the penicillin-binding proteins; alt...

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Section: Resultssupporting

confidence: 80%

Single-dose pharmacokinetics of piperacillin and tazobactam in infants and children

Reed

Goldfarb

Yamashita

et al. 1994

Antimicrob Agents Chemother

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“…c Predicted from the relationships given in Table 3. sources of variability arising from growth and development, concomitant pathophysiology, and other therapeutic regimens (15). Of the several independent variables that have been used to determine an appropriate drug dosage in children (age, BSA, BWT), drugs have generally been prescribed on the basis of BWT (drugs with wide therapeutic windows) or, to a lesser extent, BSA (drugs with narrow therapeutic windows) (19).…”

Section: Discussionmentioning

confidence: 99%

Determination of Dosing Guidelines for Stavudine (2′,3′-Didehydro-3′-Deoxythymidine) in Children with Human Immunodeficiency Virus Infection

Kaul

Kline

Church

et al. 2001

Antimicrob Agents Chemother

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The results of the development of dosing guidelines for stavudine in human immunodeficiency virus (HIV)-infected children are summarized. Included in the integrated analyses were 21 and 33 HIV-infected pediatric and adult patients, respectively, from three phase I-II studies. Data for 21 children and 18 adults who received intravenous doses of 0.125 to 2 and 0.5 to 1 mg/kg of body weight, respectively, were used for the determination of dosing guidelines; exposure data for 16 children and 15 adults who received oral doses of 1 to 2 and 0.5 to 1 mg/kg/day, respectively, were used to validate the dosing recommendations for children. Significant relationships were observed between total body clearance (in milliliters per minute) in children and adults combined and demographic parameters of age, body weight, and body surface area (R 2 ‫؍‬ 0.77 to 0.80; P ‫؍‬ 0.0001). Models of approximated pediatric dose based on clearance values and direct adult exposure yielded a stavudine dosage of 2 mg/kg/day for children of <30 kg of body weight and 1 mg/kg/day (adult dose) for children of >30 kg of body weight.

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“…En la mayor parte de los casos, la posologia y frecuencia de administration suelen calcularse de acuerdo al peso total del paciente, con poca consideration a otros factores que pueden afectar la disponibilidad de los medicamentos, especialmente en los recien nacidos 10 . El ajuste ideal de dosis deben'a considerar la edad del paciente, la maduraci6n de sus organos de metabolizacion y excreci6n del medicamento, como tambien -lo que en nuestro medio no siempre es posible-sus concentraciones plasmaticas 11 .…”

Section: Comentariounclassified