Caffeine Pharmacokinetics in Preterm Infants Older than
2 Weeks

Sa, Pearlman; Durán, Carlos G.; Ma, Wood; Mj, Maisels; Cm, Berlin

doi:10.1159/000480966

Cited by 31 publications

(15 citation statements)

References 14 publications

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“…The t 1/2 value was 65.3 hours, clearance was 0.14^0.01 ml/kg per min, and volume of distribution was 0.87^0.01 l/kg. Pearlman et al 48 measured the caffeine citrate t 1/2 in 17 preterm infants and found it to be 52.0^23.9 hours.…”

Section: Pharmacokinetics Of Caffeine Citrate In Preterm Infantsmentioning

confidence: 99%

Clinical pharmacology of caffeine citrate in preterm infants

Pacifici

2014

Medical Express

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BACKGROUND: Apnea of prematurity consists in 15 to 20 sec. of breathing cessation and is the most important disorder in the control of breathing in preterm infants. It is treated with caffeine citrate. OBJECTIVES: The objectives of this article are to review: (1) the mechanisms of action, (2) the effects, (3) the metabolism, (4) the pharmacokinetics, and (5) the adverse effects of caffeine citrate in preterms. METHODS: The bibliographic search was performed using PubMed and EMBASE databases as search engines and April 2014 was the cutoff point. RESULTS: Caffeine citrate is a stimulant of the respiratory and central nervous systems. It binds competitively to the receptors for adenosine A1 and A2 A , causing inhibition. Caffeine increases respiratory rate and minute volume, stimulates respiratory centers, and increases pulmonary blood flow and the sensitivity of central medullary areas to hypercapnia. Orally administered caffeine citrate is rapidly and completely absorbed. It is N-demethylated by CYP1A2 and is N-acetylated by N-acetyltransferase. The half-life of caffeine citrate is 100 hours at birth and 5 hours at a gestational age. 29 weeks. There is a remarkable shortening of the half-life during neonatal maturation. Adverse effects of caffeine are usually mild, and include restlessness, vomiting, and functional cardiac symptoms. CONCLUSIONS: Caffeine citrate is the drug of choice for the treatment of apnea of prematurity. It is an easy drug to use. Administered orally or intravenously once a day, it does not require monitoring of serum concentrations and has few side effects.

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Section: Pharmacokinetics Of Caffeine Citrate In Preterm Infantsmentioning

confidence: 99%

Clinical pharmacology of caffeine citrate in preterm infants

Pacifici

2014

Medical Express

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“…[43] The pharmacokinetics of caffeine, like theophylline, are highly variable in the premature neonate. [34,[44][45][46][47][48][49] Gorodischer and Karplus [44] examined pharmacokinetics of caffeine in neonates with a wide range of gestational ages (25-34 weeks). A prolonged half-life of up to 65 hours was noticed in some patients, suggesting a once daily administration regimen.…”

Section: Mechanism Of Actionmentioning

confidence: 99%

“…In another study, the half-life is reported at about 52 hours. [45] Postnatal age, weight at treatment and gestational age may contribute to variability in the clearance of caffeine. [48,49] The slower clearance in the very premature neonate is due to a decreased elimination rate and not an increase in volume of distribution (Vd), since Vd of caffeine is similar in adults and neonates.…”

Section: Mechanism Of Actionmentioning

confidence: 99%

Treatment of Apnea of Prematurity

Bhatt‐Mehta

Schumacher

2003

Pediatric Drugs

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In the last decade, knowledge regarding the neurodevelopment and functional aspects of the respiratory centers during postnatal maturation has increased substantially. However, an increase in such knowledge has not provided a basis for change in practice. The diagnosis of apnea of prematurity (AOP) is one of exclusion. All causes of secondary apnea must be ruled out before initiating treatment for AOP. Treatment will depend on the etiology as well as effectiveness and tolerability of the treatment by the patient. The primary goal of any treatment of AOP is to prevent the frequency of apnea lasting >20 seconds, and/or those that are shorter, but associated with cyanosis and bradycardia. The clinical management of AOP is not much different today than it was two decades ago, with pharmacologic and nonpharmacologic treatment options remaining the mainstay of therapy. Methylxanthines are still the most widely used pharmacologic agents. Due to the wider therapeutic index of caffeine and ease of once daily administration, it should be the preferred agent. Doxapram, or nonpharmacologic treatment measures such as nasal continuous positive airway pressure, may be considered in infants who are unresponsive to methylxanthine treatment alone. Treatment should be continued until there is complete resolution of apnea, and for some time thereafter. The choice of method for weaning treatment remains one of individual physician preference. Discharge from hospital after apnea requires close monitoring and some infants will require home apnea monitors. The decision to provide a home apnea monitor should be individualized for each patient, depending on the effectiveness of treatment and clinical response.

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“…Second, the caffeine half‐life depends on age, being longer in fetuses than in full‐term newborn infants as a result of lower enzymatic activities and the relative immaturity of the caffeine metabolic pathway, and decreases exponentially with post‐natal age (Carrier et al . 1988; Pearlman et al . 1989; Nehlig 1999).…”

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confidence: 99%

Adenosine A₁ receptor down‐regulation in mothers and fetal brain after caffeine and theophylline treatments to pregnant rats

León

Albasanz

Ruiz

et al. 2002

Journal of Neurochemistry

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Pregnant rats were treated daily with 1 g/L of caffeine or theophylline in their drinking water during pregnancy and the effect of these methylxanthines on adenosine A 1 receptor was assayed using binding and reverse transcription polymerase chain reaction (RT-PCR) assays in brains from both mothers and full-term fetuses. In plasma membranes from pregnant rat brain, caffeine and theophylline caused a significant decrease in total receptor numbers, of the same order in both cases (30%), with no significant changes on receptor affinity. The effect of these adenosine receptor antagonists on plasma membranes from fetal brains was more marked, being detected at approximately 50% of the total receptors detected in control conditions. However, in this tissue, a significant increase in the receptor affinity, of the same order in both cases, was also detected after antagonist administration. No significant variation on the potency of caffeine and theophylline as antagonists was detected after treatments in mothers; however, higher affinities were detected in fetuses. A decrease in the total receptor numbers in fetal brain was associated with an increase in the mRNA coding A 1 receptor, as determined by RT-PCR assays, not having detected any mRNA difference in maternal brain. No variation in the levels of mRNA coding A 2A receptor was detected in any case. These results suggest that maternal caffeine or theophylline intake modulates adenosine A 1 receptor, causing a downregulation of adenosine A 1 receptor in brain in both mothers and fetuses.

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Caffeine Pharmacokinetics in Preterm Infants Older than 2 Weeks

Cited by 31 publications

References 14 publications

Clinical pharmacology of caffeine citrate in preterm infants

Clinical pharmacology of caffeine citrate in preterm infants

Treatment of Apnea of Prematurity

Adenosine A₁ receptor down‐regulation in mothers and fetal brain after caffeine and theophylline treatments to pregnant rats

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Caffeine Pharmacokinetics in Preterm Infants Older than 2 Weeks

Cited by 31 publications

References 14 publications

Clinical pharmacology of caffeine citrate in preterm infants

Clinical pharmacology of caffeine citrate in preterm infants

Treatment of Apnea of Prematurity

Adenosine A1 receptor down‐regulation in mothers and fetal brain after caffeine and theophylline treatments to pregnant rats

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Adenosine A₁ receptor down‐regulation in mothers and fetal brain after caffeine and theophylline treatments to pregnant rats