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Pharmacokinetics of anti-infective agents in paediatric patients
D R Butler1, R J Kuhn, M H Chandler
1University of Kentucky Hospital, Department of Pharmacy, Lexington.
Insights
Pediatric drug disposition differs from adults, with altered pharmacokinetics for many anti-infectives. More research is needed to ensure safe and effective pediatric dosing of new antimicrobial agents.
Area of Science:
- Pharmacology
- Pediatrics
- Drug Metabolism
Background:
- Drug disposition, including volume of distribution (Vd), excretion, and elimination, varies significantly between pediatric and adult patients.
- Commonly used pediatric anti-infectives like penicillins, cephalosporins, and aminoglycosides exhibit altered pharmacokinetic profiles in children.
- Specific conditions such as cystic fibrosis, burns, and cancer can further impact drug clearance and Vd in pediatric populations.
Purpose of the Study:
- To review the existing literature on the pharmacokinetics of anti-infective agents in children.
- To highlight the differences in drug disposition between pediatric and adult populations.
- To identify knowledge gaps and emphasize the need for further research in pediatric anti-infective pharmacokinetics.
Main Methods:
- Literature review of studies investigating anti-infective pharmacokinetics in pediatric populations.
- Analysis of pharmacokinetic parameters such as volume of distribution (Vd), clearance, and elimination half-life.
- Comparison of data across different pediatric age groups and disease states.
Main Results:
- Children generally exhibit a larger volume of distribution (Vd) for many drugs compared to adults, potentially increasing elimination half-life.
- Clearance of certain drugs, like acylureido-penicillins and aminoglycosides, can be increased in pediatric patients with conditions such as cystic fibrosis, burns, or cancer.
- Limited pharmacokinetic data exist for several important anti-infectives, antivirals, and antifungals in children, with most research focusing on neonates and adults.
Conclusions:
- Significant pharmacokinetic differences necessitate careful consideration for anti-infective drug use in children.
- Current dosage guidelines may require adjustments based on individual pediatric patient conditions.
- Further pharmacokinetic studies in children are crucial for the appropriate and safe administration of the expanding range of anti-infective therapies.
Abstract:
Various differences in drug disposition exist between children and adults. For example, the volume of distribution (Vd) for many drugs is larger in children than in adults. Other parameters, including excretion and elimination may be altered in children compared with adults. The penicillins and cephalosporins are used commonly for the treatment of infection in paediatric patients. The increased Vd in children contributes to the increased elimination half-life of these agents. Clearance of the acylureido-penicillins is increased in children with cystic fibrosis, a disease that decreases the elimination half-life for these drugs. Aminoglycosides distribute into extracellular fluid and their pharmacokinetic profile is affected by changes in Vd. The Vd for aminoglycosides is slightly higher in children than in adults. Children with cystic fibrosis, burns, or cancer have higher clearance rates and larger Vd values for aminoglycosides. Few data in the literature address the pharmacokinetics of other anti-infective agents, including vancomycin, teicoplanin, erythromycin, metronidazole, chloramphenicol, and cotrimoxazole (trimethoprim-sulfamethoxazole), in children. Similarly, there is little information regarding the pharmacokinetic profile of antivirals and antifungals in children. Dosage guidelines are available to enable the clinician to initiate anti-infective therapy in children. Subsequent dosage requirements may change based on the patient's current clinical condition. Although several studies have investigated the pharmacokinetics of anti-infectives in neonates and adults, data for children are limited. Therefore, further studies are required so that the ever growing arsenal of anti-infectives can be administered appropriately to children.