The evaluation of a new chemical entity for use in pediatric populations, while normally a development afterthought, can be successfully accomplished early in a clinical program by careful foreplanning utilizing available development program tools. Compassionate use programs provide an excellent framework for the collection of safety, tolerability, and pharmacokinetic data in pediatric populations. The conduct of formal pharmacokinetic studies in children may proceed in parallel with pediatric efficacy studies, if appropriately designed and staged. Additional collection of meaningful and predictive pharmacokinetic specimens may be accomplished in children without the need for repeated phlebotomy. Careful selection of target populations for pharmacokinetic research in children may expedite rapid drug development of pediatric indications. Utilizing these techniques, a pediatric clinical development program may be prosecuted with minimal prior adult data and synchronous with the overall clinical development program.
McKinlayMAPevearDCRossmannMGTreatment of the Picornavirus common cold by inhibitors of viral uncoating and attachment. Ann Rev Microbiology. 1992;46:635–654.
5.
SmithTJKremerMJLuoMVriendGArnoldEKramerGRossmannMGMcKinlayMADianaGOttoMJThe site of attachment of human rhinovirus 14 and antiviral agents that inhibit uncoating. Science. 1986;233:1286–1293.
6.
O'ConnellJAlbinABlumDGrintPSchwartzJ.Development of antiviral agents for Picornavirus infections. In RotbartHA, ed. Human Enterovirus Infections. Washington, DC: ASM Press; 1995;419–434.
7.
DianaGDPevearDCAntipicornavirus drugs: Current status. Antiviral Chemistry Chemother. 1997;8: 412–418.
8.
RogersJMDianaGDMcKinlayMAPleconaril, a broad spectrum antipicornaviral agent. In MillsJCoreyL, eds. Antiviral Chemotherapy: New Directions for Clinical Application and Research. Englewood Cliffs, NJ: PTR Prentice-Hall; 1998.
9.
HaydenFGAndriesAJanssenPAJSafety and efficacy of oral pirodavir (R 77975) in experimental rhinovirus infection. Antimicrobial Agents Chemother. 1992;36:727–732.
10.
SchiffGMSherwoodJRYoungECMasonLJProphylactic efficacy of WIN 54954 in prevention of experimental human coxsackievirus A21 infection and illness. Antiviral Res.1992;17(Suppl 1):92.
11.
TurnerRBDutkoFJGoldsteinNHLockwoodGHaydenFGEfficacy of oral WIN 54954 for the prophylaxis of experimental rhinovirus infection. Antimicrobial Agents Chemother. 1993;37:297–300.
12.
DianaGDRudewiczPPevearDCNitzTJAldousSCPicornavirus inhibitors: triflouromethyl substitution provides a global protective effect against hepatic metabolism. J Medicinal Chemistry. 1995;38:1355–1371.
13.
PevearDCSeipelMEPallanschMAMcKinlayMAIn vitro activity of VP 63843 against field isolates of non-polio enteroviruses. H-99 Presented at the 36th Interscience Conference on Antimicrobial Agents and Chemotherapy, New Orleans, LA, September 15–18, 1996.
14.
RotbartHAJonesANovelliVBlancheSWebsterADBPleconaril treatment of chronic enteroviral central nervous system infections in children with agammaglobulinemia. Presented at the 37th Interscience Conference on Antimicrobial Agents and Chemotherapy, Toronto, Ontario, Canada, September 28-October 1, 1997.
15.
McKinneyRAKatzSLWilfertKMChronic enteroviral meningoencephalitis in agammagolbuliemic patients. Rev Infectious Dis.1987;9:334–356.
16.
WebsterADBRotbartHAWarnerTRudgePHymanN.Diagnosis of enterovirus brain disease in hypogammaglobulinemic patients by polymerase chain reaction. Clinical Infectious Dis.1993;17:657–661.
17.
AbzugMJLevinMJRotbartHAProfile of enterovirus disease in the first two weeks of life. Pediatric Infectious Dis J.1993;12:820–824.
18.
JenistaJAPowellKRMenegusMAEpidemiology of neonatal enterovirus infection. J Pediatrics. 1984;104:685–690.
19.
ModlinJFPerinatal echovirus infection: insights from a literature review of 61 cases. Western J Med.1986;138:847–851.
20.
KearnsGLBradleyJSAbdel-RahmanSJacobsRFPharmacokinetics of pleconaril in neonates. Submitted for presentation at the American Society of Clinical Pharmacology and Therapeutics, San Diego, CA June 6–11, 1999.
21.
JohnsonSLCommunity study of the role of viral infections of asthma in 9–11 year old children. Br Med J.1995;310:1225–1228.
22.
NicholsonKGRespiratory viruses and exacerbations of asthma in adults. Br Med J.1991;307: 982–987.
23.
CarlsenKHRespiratory virus infections and aeroallergens in acute bronchial asthma. Arch Dis Childhood. 1984;59:310–315.
24.
JohnsonSLNatural and experimental rhinovirus infections of the lower respiratory tract. Am J Respiratory Critical Care Med.1995;152:546–552.
25.
KearnsGLIntroduction: Drug development for infants and children: Rescuing the therapeutic orphan. Drug Inf J.1996;30:1121–1123.
26.
AdlerJLEpidemilogic investigation of hand, foot and mouth disease. Am J Dis Children. 1970;120:309–131.
27.
HughesROHand, foot and mouth disease associated with Coxsackie A9 virus. Lancet. 1972;11:751–752.
28.
JohnsonJMNosocomial outbreak of hand-foot-and-mouth disease among operating suite personnel. Infection Control. 1986;7:172–176.
29.
KimuraAKLight and microscopic study of skin lesions of subjects with hand, foot and mouth disease. Tohoku J Experimen Med.1977;122:237–247.
30.
LindenbaumJEHand, foot and mouth disease associated with coxsackievirus group B. Scandinavian J Infectious Dis.1975;7:161–163.
MukerjiPS Hand, foot and mouth disease in two Edinburgh practices, 1980. J Royal Coll Gen Practitioners. 1982;32:366–368.
33.
NahmiasAJGeneralized eruption in a child with eczema due to coxsackievirus A16. Arch Dermatol. 1968;97:147–148.
34.
RobinsonCRReport of an outbreak of febrile illness with pharyngeal lesions and exanthem: Toronto, summer 1957—isolation of group A Coxsackie virus. Canadian Med Assoc J.1958;79:615–621.
35.
Anonymous. Outbreak of hand, foot and mouth disease in Sarawak. Cluster of deaths among infants and young children. Weekly Epidemiolog Rev.1997;72:211–212.
36.
Anonymous. Deaths among children during an outbreak of hand, foot and mouth disease—Taiwan, Republic of China, April-July 1998. Morbidity Mortality Weekly Report. 1998;47:629–632.
37.
KearnsGLWellsTGPharmacokinetics of pleconaril in children. Abstract A-206. Presented at the 99th Annual Meeting of the American Society of Clinical Pharmacology and Therapeutics. New Orleans, LA, March 30-April 1, 1998.
