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Clinical Pharmacokinetics
Published in: Clinical Pharmacokinetics 2/2016

01-02-2016 | Review Article

Challenges Associated with Route of Administration in Neonatal Drug Delivery

Authors: Matthew W. Linakis, Jessica K. Roberts, Anita C. Lala, Michael G. Spigarelli, Natalie J. Medlicott, David M. Reith, Robert M. Ward, Catherine M. T. Sherwin

Published in: Clinical Pharmacokinetics | Issue 2/2016

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Abstract

The administration of drugs to neonates poses significant challenges. The aim of this review was to provide insight into some of these challenges and resolutions that may be encountered with several of the most commonly used routes of administration and dosage forms in neonatal care, including oral, parenteral, transdermal, intrapulmonary, and rectal. Important considerations include fluctuations in stomach pH hours to years after birth, the logistics of setting up an intravenous infusion, the need for reduced particle size for aerosol delivery to the developing neonatal lung, and variation in perirectal venous drainage. Additionally, some of the recently developed technologies for use in neonatal care are described. While the understanding of neonatal drug delivery has advanced over the past several decades, there is still a deficiency of technologies and formulations developed specifically for this population.
Literature
1.
Khatri N, Misra A. Applications of polymers in parenteral drug delivery. In: Misra A, Shahiwala A, editors. Applications of polymers in drug delivery. Shrewsbury: Smithers Rapra; 2014.
2.
Development of paediatric medicines: points to consider in formulation annex 5. WHO Technical Report Series. Geneva: World Health Organization; 2012. p. 1–29.
3.
Pein M, Preis M, Eckert C, Kiene FE. Taste-masking assessment of solid oral dosage forms—a critical review. Int J Pharm. 2014;465(1–2):239–54.PubMedCrossRef
4.
Maniruzzaman M, Boateng JS, Chowdhry BZ, Snowden MJ, Douroumis D. A review on the taste masking of bitter APIs: hot-melt extrusion (HME) evaluation. Drug Dev Ind Pharm. 2014;40(2):145–56.PubMedCrossRef
5.
Papai K, Budai M, Ludanyi K, Antal I, Klebovich I. In vitro food–drug interaction study: which milk component has a decreasing effect on the bioavailability of ciprofloxacin? J Pharm Biomed Anal. 2010;52(1):37–42.PubMedCrossRef
6.
Knippa A. PN nursing care of children. Stilwell (KS): Assessment Technologies Institute; 2011.
7.
Klingmann V. Acceptability testing of minitablets from neonates to pre-school children. 6th European Paediatric Formulation Initiative Conference; 17–18 Sep 2014; Athens.
8.
Avery GB, Randolph JG, Weaver T. Gastric acidity in the first day of life. Pediatrics. 1966;37(6):1005–7.PubMed
9.
Tayman C, Rayyan M, Allegaert K. Neonatal pharmacology: extensive interindividual variability despite limited size. J Pediatr Pharmacol Ther. 2011;16(3):170–84.PubMedCentralPubMed
10.
11.
Kearns GL, Abdel-Rahman SM, Alander SW, Blowey DL, Leeder JS, Kauffman RE. Developmental pharmacology: drug disposition, action, and therapy in infants and children. N Engl J Med. 2003;349(12):1157–67.PubMedCrossRef
12.
Bartelink IH, Rademaker CM, Schobben AF, van den Anker JN. Guidelines on paediatric dosing on the basis of developmental physiology and pharmacokinetic considerations. Clin Pharmacokinet. 2006;45(11):1077–97.PubMedCrossRef
13.
Marsot A, Brevaut-Malaty V, Vialet R, Boulamery A, Bruguerolle B, Simon N. Pharmacokinetics and absolute bioavailability of phenobarbital in neonates and young infants: a population pharmacokinetic modelling approach. Fundam Clin Pharmacol. 2014;28(4):465–71.PubMedCrossRef
14.
Silverio J, Poole JW. Serum concentrations of ampicillin in newborn infants after oral administration. Pediatrics. 1973;51(3):578–80.PubMed
15.
Koren G. Therapeutic drug monitoring principles in the neonate. National Academy of Clinical Biochemistry. Clin Chem. 1997;43(1):222–7.PubMed
16.
Carlos MA, Babyn PS, Marcon MA, Moore AM. Changes in gastric emptying in early postnatal life. J Pediatr. 1997;130(6):931–7.PubMedCrossRef
17.
Czinn SJ, Blanchard S. Gastroesophageal reflux disease in neonates and infants: when and how to treat. Paediatr Drugs. 2013;15(1):19–27.PubMedCrossRef
18.
Hillemeier AC, Lange R, McCallum R, Seashore J, Gryboski J. Delayed gastric emptying in infants with gastroesophageal reflux. J Pediatr. 1981;98(2):190–3.PubMedCrossRef
19.
Martinussen M, Brubakk AM, Linker DT, Vik T, Yao AC. Mesenteric blood flow velocity and its relation to circulatory adaptation during the first week of life in healthy term infants. Pediatr Res. 1994;36(3):334–9.PubMedCrossRef
20.
Martinussen M, Brubakk AM, Vik T, Yao AC. Mesenteric blood flow velocity and its relation to transitional circulatory adaptation in appropriate for gestational age preterm infants. Pediatr Res. 1996;39(2):275–80.PubMedCrossRef
21.
Nankervis CA, Giannone PJ, Reber KM. The neonatal intestinal vasculature: contributing factors to necrotizing enterocolitis. Semin Perinatol. 2008;32(2):83–91.PubMedCrossRef
22.
Reber KM, Mager GM, Miller CE, Nowicki PT. Relationship between flow rate and NO production in postnatal mesenteric arteries. Am J Physiol Gastrointest Liver Physiol. 2001;280(1):G43–50.PubMed
23.
Nankervis CA, Nowicki PT. Role of nitric oxide in regulation of vascular resistance in postnatal intestine. Am J Physiol. 1995;268(6 Pt 1):G949–58.PubMed
24.
Reed MD. The ontogeny of drug disposition: focus on drug absorption, distribution, and excretion. Drug Inf J. 1996;30:1129–34.
25.
Shankaran S, Kauffman RE. Use of chloramphenicol palmitate in neonates. J Pediatr. 1984;105(1):113–6.PubMedCrossRef
26.
27.
Hill JM, Maloney A, Stephens K, Adrezin RS, Eisenfeld L. Stethoscope for monitoring neonatal abdominal sounds. Int J Mod Eng. 2008;9(1):5.
28.
Dumas J, Hill KM, Adrezin RS, et al. Feasibility of an electronic stethoscope system for monitoring neonatal bowel sounds. Conn Med. 2013;77(8):467–71.PubMed
29.
van Kalken CK, Giaccone G, van der Valk P, et al. Multidrug resistance gene (P-glycoprotein) expression in the human fetus. Am J Pathol. 1992;141(5):1063–72.PubMedCentralPubMed
30.
Boucher FD, Modlin JF, Weller S, et al. Phase I evaluation of zidovudine administered to infants exposed at birth to the human immunodeficiency virus. J Pediatr. 1993;122(1):137–44.PubMedCrossRef
31.
Capparelli EV, Mirochnick M, Dankner WM, et al. Pharmacokinetics and tolerance of zidovudine in preterm infants. J Pediatr. 2003;142(1):47–52.PubMedCrossRef
32.
Wu CY, Benet LZ, Hebert MF, et al. Differentiation of absorption and first-pass gut and hepatic metabolism in humans: studies with cyclosporine. Clin Pharmacol Ther. 1995;58(5):492–7.PubMedCrossRef
33.
Paine MF, Shen DD, Kunze KL, et al. First-pass metabolism of midazolam by the human intestine. Clin Pharmacol Ther. 1996;60(1):14–24.PubMedCrossRef
34.
Ince I, Knibbe CA, Danhof M, de Wildt SN. Developmental changes in the expression and function of cytochrome P450 3A isoforms: evidence from in vitro and in vivo investigations. Clin Pharmacokinet. 2013;52(5):333–45.PubMedCrossRef
35.
de Wildt SN, Kearns GL, Hop WC, Murry DJ, Abdel-Rahman SM, van den Anker JN. Pharmacokinetics and metabolism of oral midazolam in preterm infants. Br J Clin Pharmacol. 2002;53(4):390–2.PubMedCentralPubMedCrossRef
36.
37.
38.
Aagaard K, Ma J, Antony KM, Ganu R, Petrosino J, Versalovic J. The placenta harbors a unique microbiome. Sci Transl Med. 2014;6(237):237ra65.PubMedCrossRef
39.
Adlerberth I, Wold AE. Establishment of the gut microbiota in Western infants. Acta Paediatr. 2009;98(2):229–38.PubMedCrossRef
40.
Scholtens PA, Oozeer R, Martin R, Amor KB, Knol J. The early settlers: intestinal microbiology in early life. Annu Rev Food Sci Technol. 2012;3:425–47.PubMedCrossRef
41.
Stewart CJ, Marrs EC, Nelson A, et al. Development of the preterm gut microbiome in twins at risk of necrotising enterocolitis and sepsis. PLoS One. 2013;8(8):e73465.PubMedCentralPubMedCrossRef
42.
Peppercorn MA, Goldman P. The role of intestinal bacteria in the metabolism of salicylazosulfapyridine. J Pharmacol Exp Ther. 1972;181(3):555–62.PubMed
43.
Saha JR, Butler VP Jr, Neu HC, Lindenbaum J. Digoxin-inactivating bacteria: identification in human gut flora. Science. 1983;220(4594):325–7.PubMedCrossRef
44.
Lindenbaum J, Rund DG, Butler VP Jr, Tse-Eng D, Saha JR. Inactivation of digoxin by the gut flora: reversal by antibiotic therapy. N Engl J Med. 1981;305(14):789–94.PubMedCrossRef
45.
Carmody RN, Turnbaugh PJ. Host–microbial interactions in the metabolism of therapeutic and diet-derived xenobiotics. J Clin Invest. 2014;124(10):4173–81.PubMedCentralPubMedCrossRef
46.
Broussard L. Small size, big risk: preventing neonatal and pediatric medication errors. Nurs Womens Health. 2010;14(5):405–8.PubMedCrossRef
47.
D’Antonio YC, Cohen MR. Pediatric medication errors. In: Cohen MR, editor. Medication errors: causes, prevention, and risk management. Sudbury (MA): Jones and Bartlett Publishers, Inc.; 1999.
48.
49.
Allegaert K, Vanhaesebrouck S, Kulo A, et al. Prospective assessment of short-term propylene glycol tolerance in neonates. Arch Dis Child. 2010;95(12):1054–8.PubMedCrossRef
50.
Salunke S, Brandys B, Giacoia G, Tuleu C. The STEP (Safety and Toxicity of Excipients for Paediatrics) database: part 2—the pilot version. Int J Pharm. 2013;457(1):310–22.PubMedCrossRef
51.
Turner MA, Duncan J, Shah U, et al. European study of neonatal exposure to excipients: an update. Int J Pharm. 2013;457(1):357–8.PubMedCrossRef
52.
Stiers JL, Ward RM. Newborns, one of the last therapeutic orphans to be adopted. JAMA Pediatr. 2014;168(2):106–8.PubMedCrossRef
53.
Usher R, Shephard M, Lind J. The blood volume of the newborn infant and placental transfusion. Acta Paediatr. 1963;52:497–512.PubMedCrossRef
54.
Sherwin CM, Medlicott NJ, Reith DM, Broadbent RS. Intravenous drug delivery in neonates: lessons learnt. Arch Dis Child. 2014;99(6):590–4.PubMedCrossRef
55.
Sherwin CM, McCaffrey F, Broadbent RS, Reith DM, Medlicott NJ. Discrepancies between predicted and observed rates of intravenous gentamicin delivery for neonates. J Pharm Pharmacol. 2009;61(4):465–71.PubMedCrossRef
56.
Medlicott NJ, Reith DM, McCaffrey F, Krittaphol W, Broadbent RS. Delayed delivery of intravenous gentamicin in neonates: impact of infusion variables. J Pharm Pharmacol. 2013;65(3):370–8.PubMedCrossRef
57.
Colacchio K, Deng Y, Northrup V, Bizzarro MJ. Complications associated with central and non-central venous catheters in a neonatal intensive care unit. J Perinatol. 2012;32(12):941–6.PubMedCrossRef
58.
Katheria AC, Fleming SE, Kim JH. A randomized controlled trial of ultrasound-guided peripherally inserted central catheters compared with standard radiograph in neonates. J Perinatol. 2013;33(10):791–4.PubMedCrossRef
59.
Panagiotounakou P, Antonogeorgos G, Gounari E, Papadakis S, Labadaridis J, Gounaris AK. Peripherally inserted central venous catheters: frequency of complications in premature newborn depends on the insertion site. J Perinatol. 2014;34(6):461–3.PubMedCrossRef
60.
Bradley JS, Wassel RT, Lee L, Nambiar S. Intravenous ceftriaxone and calcium in the neonate: assessing the risk for cardiopulmonary adverse events. Pediatrics. 2009;123(4):e609–13.PubMedCrossRef
61.
Evans C, Dixon A. Intravenous therapy: practice issues. Infant. 2006;2(4):133–6.
62.
Robinson CA, Sawyer JE. Y-site compatibility of medications with parenteral nutrition. J Pediatr Pharmacol Ther. 2009;14(1):48–56.PubMedCentralPubMed
63.
Kenner C, Lott JW. Comprehensive neonatal care: an interdisciplinary approach. 4th ed. St. Louis (MO): Elsevier Health Sciences; 2007.
64.
Jew RK, Owen D, Kaufman D, Balmer D. Osmolality of commonly used medications and formulas in the neonatal intensive care unit. Nutr Clin Pract. 1997;12(4):158–63.CrossRef
65.
Alade SL, Brown RE, Paquet A Jr. Polysorbate 80 and E-Ferol toxicity. Pediatrics. 1986;77(4):593–7.PubMed
66.
Gershanik J, Boecler B, Ensley H, McCloskey S, George W. The gasping syndrome and benzyl alcohol poisoning. N Engl J Med. 1982;307(22):1384–8.PubMedCrossRef
67.
Ward RM, Kern SE. Clinical trials in neonates: a therapeutic imperative. Clin Pharmacol Ther. 2009;86(6):585–7.PubMedCrossRef
68.
Uppal N, Yasseen B, Seto W, Parshuram CS. Drug formulations that require less than 0.1 mL of stock solution to prepare doses for infants and children. CMAJ. 2011;183(4):E246–8.PubMedCentralPubMedCrossRef
69.
Strolin Benedetti M, Baltes EL. Drug metabolism and disposition in children. Fundam Clin Pharmacol. 2003;17(3):281–99.PubMedCrossRef
70.
National Center for Immunization and Respiratory Diseases. General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2011;60(RR2):1–64.
71.
Khambalia AZ, Roberts CL, Bowen JR, Nassar N. Maternal and infant characteristics by mode of vitamin K prophylaxis administration. J Paediatr Child Health. 2012;48(8):665–8.PubMedCrossRef
72.
Ipema HJ. Use of oral vitamin K for prevention of late vitamin k deficiency bleeding in neonates when injectable vitamin K is not available. Ann Pharmacother. 2012;46(6):879–83.PubMedCrossRef
73.
Bellieni CV, Aloisi AM, Ceccarelli D, et al. Intramuscular injections in newborns: analgesic treatment and sex-linked response. J Matern Fetal Neonatal Med. 2013;26(4):419–22.PubMedCrossRef
74.
Patel IH, Weinfeld RE, Konikoff J, Parsonnet M. Pharmacokinetics and tolerance of ceftriaxone in humans after single-dose intramuscular administration in water and lidocaine diluents. Antimicrob Agents Chemother. 1982;21(6):957–62.PubMedCentralPubMedCrossRef
75.
Powell KR, Mawhorter SD. Outpatient treatment of serious infections in infants and children with ceftriaxone. J Pediatr. 1987;110(6):898–901.PubMedCrossRef
76.
Shah VS, Taddio A, Hancock R, Shah P, Ohlsson A. Topical amethocaine gel 4% for intramuscular injection in term neonates: a double-blind, placebo-controlled, randomized trial. Clin Ther. 2008;30(1):166–74.PubMedCrossRef
77.
Liaw JJ, Zeng WP, Yang L, Yuh YS, Yin T, Yang MH. Nonnutritive sucking and oral sucrose relieve neonatal pain during intramuscular injection of hepatitis vaccine. J Pain Symptom Manag. 2011;42(6):918–30.CrossRef
78.
Hensel D, Morson GL, Preuss EA. Best practices in newborn injections. MCN Am J Matern Child Nurs. 2013;38(3):163–7 (quiz 168–169).PubMedCrossRef
79.
Ohls RK, Ehrenkranz RA, Wright LL, et al. Effects of early erythropoietin therapy on the transfusion requirements of preterm infants below 1250 grams birth weight: a multicenter, randomized, controlled trial. Pediatrics. 2001;108(4):934–42.PubMedCrossRef
80.
Costa S, Romagnoli C, Zuppa AA, et al. How to administrate erythropoietin, intravenous or subcutaneous? Acta Paediatr. 2013;102(6):579–83.PubMedCrossRef
81.
Ghadially R, Shear NH. Topical therapy and percutaneous absorption. In: Fletcher J, editor. Pediatric pharmacology: therapeutic principles in practice. 2nd ed. Philadelphia: W.B. Saunders Company; 1992. p. 72–7.
82.
83.
Kearns GL. Impact of developmental pharmacology on pediatric study design: overcoming the challenges. J Allergy Clin Immunol. 2000;106(3 Suppl):S128–38.PubMedCrossRef
84.
West DP, Worobec S, Solomon LM. Pharmacology and toxicology of infant skin. J Investig Dermatol. 1981;76(3):147–50.PubMedCrossRef
85.
Powell H, Swarner O, Gluck L, Lampert P. Hexachlorophene myelinopathy in premature infants. J Pediatr. 1973;82(6):976–81.PubMedCrossRef
86.
87.
88.
Amirav I, Newhouse MT. Aerosol therapy in infants and toddlers: past, present and future. Expert Rev Respir Med. 2008;2(5):597–605.PubMedCrossRef
89.
Amirav I, Newhouse MT. Deposition of small particles in the developing lung. Paediatr Respir Rev. 2012;13(2):73–8.PubMedCrossRef
90.
Schuepp KG, Jauernig J, Janssens HM, et al. In vitro determination of the optimal particle size for nebulized aerosol delivery to infants. J Aerosol Med. 2005;18(2):225–35.PubMedCrossRef
91.
Kohler E, Jilg G, Avenarius S, Jorch G. Lung deposition after inhalation with various nebulisers in preterm infants. Arch Dis Child Fetal Neonatal Ed. 2008;93(4):F275–9.PubMedCrossRef
92.
Fok TF, Monkman S, Dolovich M, et al. Efficiency of aerosol medication delivery from a metered dose inhaler versus jet nebulizer in infants with bronchopulmonary dysplasia. Pediatr Pulmonol. 1996;21(5):301–9.PubMedCrossRef
93.
Sood BG, Peterson J, Malian M, et al. Jet nebulization of prostaglandin E1 during neonatal mechanical ventilation: stability, emitted dose and aerosol particle size. Pharmacol Res. 2007;56(6):531–41.PubMedCentralPubMedCrossRef
94.
Fink JB. Delivery of inhaled drugs for infants and small children: a commentary on present and future needs. Clin Ther. 2012;34(11):S36–45.PubMedCrossRef
95.
Ballard J, Lugo RA, Salyer JW. A survey of albuterol administration practices in intubated patients in the neonatal intensive care unit. Respir Care. 2002;47(1):31–8.PubMed
96.
Lugo RA, Kenney JK, Keenan J, Salyer JW, Ballard J, Ward RM. Albuterol delivery in a neonatal ventilated lung model: nebulization versus chlorofluorocarbon- and hydrofluoroalkane-pressurized metered dose inhalers. Pediatr Pulmonol. 2001;31(3):247–54.PubMedCrossRef
97.
Fok TF, Lam K, Ng PC, et al. Delivery of salbutamol to nonventilated preterm infants by metered-dose inhaler, jet nebulizer, and ultrasonic nebulizer. Eur Respir J. 1998;12(1):159–64.PubMedCrossRef
98.
Engle WA. Surfactant-replacement therapy for respiratory distress in the preterm and term neonate. Pediatrics. 2008;121(2):419–32.PubMedCrossRef
99.
El-Gendy N, Kaviratna A, Berkland C, Dhar P. Delivery and performance of surfactant replacement therapies to treat pulmonary disorders. Ther Deliv. 2013;4(8):951–80.PubMedCrossRef
100.
Sweet DG, Halliday HL. The use of surfactants in 2009. Arch Dis Child Educ Pract Ed. 2009;94(3):78–83.PubMedCrossRef
101.
Nimmo AJ, Carstairs JR, Patole SK, Whitehall J, Davidson K, Vink R. Intratracheal administration of glucocorticoids using surfactant as a vehicle. Clin Exp Pharmacol Physiol. 2002;29(8):661–5.PubMedCrossRef
102.
Hughes WT, Sillos EM, LaFon S, et al. Effects of aerosolized synthetic surfactant, atovaquone, and the combination of these on murine Pneumocystis carinii pneumonia. J Infect Dis. 1998;177(4):1046–56.PubMedCrossRef
103.
van’t Veen A, Mouton JW, Gommers D, Lachmann B. Pulmonary surfactant as vehicle for intratracheally instilled tobramycin in mice infected with Klebsiella pneumoniae. Br J Pharmacol. 1996;119(6):1145–8.PubMedCentralPubMedCrossRef
104.
Yeh TF, Lin HC, Chang CH, et al. Early intratracheal instillation of budesonide using surfactant as a vehicle to prevent chronic lung disease in preterm infants: a pilot study. Pediatrics. 2008;121(5):e1310–8.PubMedCrossRef
105.
Ari A, Restrepo RD. Aerosol delivery device selection for spontaneously breathing patients: 2012. Respir Care. 2012;57(4):613–26.PubMedCrossRef
106.
107.
Murakami G, Igarashi T, Adachi Y, et al. Measurement of bronchial hyperreactivity in infants and preschool children using a new method. Ann Allergy. 1990;64(4):383–7.PubMed
108.
Moss ML. The veloepiglottic sphincter and obligate nose breathing in the neonate. J Pediatr. 1965;67(2):330–1.CrossRef
109.
Djupesland PG, Skretting A, Winderen M, Holand T. Bi-directional nasal delivery of aerosols can prevent lung deposition. J Aerosol Med. 2004;17(3):249–59.PubMedCrossRef
110.
Guerin C, Fassier T, Bayle F, Lemasson S, Richard JC. Inhaled bronchodilator administration during mechanical ventilation: how to optimize it, and for which clinical benefit? J Aerosol Med Pulm Drug Deliv. 2008;21(1):85–96.PubMedCrossRef
111.
Fink JB, Dhand R, Duarte AG, Jenne JW, Tobin MJ. Aerosol delivery from a metered-dose inhaler during mechanical ventilation. An in vitro model. Am J Respir Crit Care Med. 1996;154(2 Pt 1):382–7.PubMedCrossRef
112.
Hess DR, Dillman C, Kacmarek RM. In vitro evaluation of aerosol bronchodilator delivery during mechanical ventilation: pressure-control vs. volume control ventilation. Intensive Care Med. 2003;29(7):1145–50.PubMedCrossRef
113.
114.
Diot P, Morra L, Smaldone GC. Albuterol delivery in a model of mechanical ventilation. Comparison of metered-dose inhaler and nebulizer efficiency. Am J Respir Crit Care Med. 1995;152(4 Pt 1):1391–4.PubMedCrossRef
115.
Fink JB, Dhand R, Grychowski J, Fahey PJ, Tobin MJ. Reconciling in vitro and in vivo measurements of aerosol delivery from a metered-dose inhaler during mechanical ventilation and defining efficiency-enhancing factors. Am J Respir Crit Care Med. 1999;159(1):63–8.PubMedCrossRef
116.
Sood BG, Latif Z, Shen Y, et al. Aerosol delivery during high frequency jet ventilation: an MRI evaluation. Respir Care. 2012;57(11):1901–7.PubMedCrossRef
117.
Baleine J, Milesi C, Mesnage R, et al. Intubation in the delivery room: experience with nasal midazolam. Early Hum Dev. 2014;90(1):39–43.PubMedCrossRef
118.
Sharma R, Harish R. Comparative study on the efficacy of intranasal midazolam vs intravenous midazolam in convulsing neonates and children. Res Rev J Med Health Sci. 2013;2(4):54–7.
119.
Chiaretti A, Barone G, Rigante D, et al. Intranasal lidocaine and midazolam for procedural sedation in children. Arch Dis Child. 2011;96(2):160–3.PubMedCrossRef
120.
Keane EF. Another way to administer antiepileptic medications in infants and children. MCN Am J Matern Child Nurs. 1993;18(5):270–4.PubMedCrossRef
121.
Graves NM, Kriel RL. Rectal administration of antiepileptic drugs in children. Pediatr Neurol. 1987;3(6):321–6.PubMedCrossRef
122.
van Lingen RA, Deinum JT, Quak JM, et al. Pharmacokinetics and metabolism of rectally administered paracetamol in preterm neonates. Arch Dis Child Fetal Neonatal Ed. 1999;80(1):F59–63.PubMedCentralPubMedCrossRef
123.
Anderson BJ, Holford NH, Woolard GA. Paracetamol kinetics in neonates. Anaesth Intensive Care. 1997;25:721–2.
124.
125.
Keinanen S, Hietula M, Simila S, Kouvalainen K. Antipyretic therapy. Comparison of rectal and oral paracetamol. Eur J Clin Pharmacol. 1977;12(1):77–80.PubMedCrossRef
126.
Arana A, Morton NS, Hansen TG. Treatment with paracetamol in infants. Acta Anaesthesiol Scand. 2001;45(1):20–9.PubMedCrossRef
127.
Anderson BJ, Woollard GA, Holford NH. A model for size and age changes in the pharmacokinetics of paracetamol in neonates, infants and children. Br J Clin Pharmacol. 2000;50(2):125–34.PubMedCentralPubMedCrossRef
128.
Zuo XC, Ng CM, Barrett JS, et al. Effects of CYP3A4 and CYP3A5 polymorphisms on tacrolimus pharmacokinetics in Chinese adult renal transplant recipients: a population pharmacokinetic analysis. Pharmacogenet Genomics. 2013;23(5):251–61.PubMedCrossRef
129.
Slomkowski S, Aleman JV, Gilbert RG, et al. Terminology of polymers and polymerization processes in dispersed systems (IUPAC recommendations 2011). Pure Appl Chem. 2011;83(12):2229–59.CrossRef
130.
Amirav I, Newhouse MT, Luder A, Halamish A, Omar H, Gorenberg M. Feasibility of aerosol drug delivery to sleeping infants: a prospective observational study. BMJ Open. 2014;4(3):e004124.PubMedCentralPubMedCrossRef
131.
Dvorak M. Medicine dispensing pacifier. US Patent 5,512,047; 1996.
132.
Noble DE. Medication dispensing pacifier. US Patent 5,078,734; 1992.
133.
Luehne-Porath L. Medicine dispensing pacifier. US Patent D445,902; 2001.
134.
Dumont KE, Dumont D. Medication dispensing pacifier. US Patent D476,085; 2003.
135.
Brenner V. Infant medicine dispenser. US Patent 2,013,009,0595; 2013.
136.
Walsh J, Bickmann D, Breitkreutz J, Chariot-Goulet M. Delivery devices for the administration of paediatric formulations: overview of current practice, challenges and recent developments. Int J Pharm. 2011;415(1–2):221–31.PubMedCrossRef
137.
Kraus DM, Stohlmeyer LA, Hannon PR, Freels SA. Effectiveness and infant acceptance of the Rx medibottle versus the oral syringe. Pharmacotherapy. 2001;21(4):416–23.PubMedCrossRef
138.
Purswani MU, Radhakrishnan J, Irfan KR, Walter-Glickman C, Hagmann S, Neugebauer R. Infant acceptance of a bitter-tasting liquid medication: a randomized controlled trial comparing the Rx medibottle with an oral syringe. Arch Pediatr Adolesc Med. 2009;163(2):186–8.PubMedCrossRef
139.
Foinard A, Decaudin B, Barthelemy C, Debaene B, Odou P. Prevention of drug delivery disturbances during continuous intravenous infusion: an in vitro study on a new multi-lumen infusion access device. Ann Fr Anesth Reanim. 2013;32(9):e107–12.PubMedCrossRef
140.
World Health Organization. Report of the informal expert meeting on dosage forms of medicines for children. Geneva: World Health Organization; 2008.
141.
Kayitare E, Vervaet C, Ntawukulilyayo JD, Seminega B, Bortel V, Remon JP. Development of fixed dose combination tablets containing zidovudine and lamivudine for paediatric applications. Int J Pharm. 2009;370(1–2):41–6.PubMedCrossRef
142.
143.
Huang NN, High RH. Comparison of serum levels following the administration of oral and parenteral preparations of penicillin to infants and children of various age groups. J Pediatr. 1953;42(6):657–8.PubMedCrossRef
Metadata
Title
Challenges Associated with Route of Administration in Neonatal Drug Delivery
Authors
Matthew W. Linakis
Jessica K. Roberts
Anita C. Lala
Michael G. Spigarelli
Natalie J. Medlicott
David M. Reith
Robert M. Ward
Catherine M. T. Sherwin
Publication date
01-02-2016
Publisher
Springer International Publishing
Published in
Clinical Pharmacokinetics / Issue 2/2016
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI
https://doi.org/10.1007/s40262-015-0313-z

Other articles of this Issue 2/2016

Clinical Pharmacokinetics 2/2016 Go to the issue

Original Research Article

Pharmacokinetics and Safety of Single Intravenous Doses of JNJ-54452840, an Anti-β1-Adrenergic Receptor Antibody Cyclopeptide, in Healthy Male Japanese and Caucasian Participants

Review Article

Alternative Sampling Strategies for Cytochrome P450 Phenotyping

Review Article

Reliability of In Vitro and In Vivo Methods for Predicting the Effect of P-Glycoprotein on the Delivery of Antidepressants to the Brain

Review Article

Drug–Drug Interactions with the NS3/4A Protease Inhibitor Simeprevir

Original Research Article

Population Pharmacokinetic Modeling of Canagliflozin in Healthy Volunteers and Patients with Type 2 Diabetes Mellitus

Original Research Article

Effects of Cytochrome P450 3A4 Inhibitors—Ketoconazole and Erythromycin—on Bitopertin Pharmacokinetics and Comparison with Physiologically Based Modelling Predictions