Pharmacokinetic profile of caffeine in the premature newborn infant with apnea

Aranda, Jacob V.; Cook, Clarence; Gorman, Winifred; Collinge, Judith M.; Loughnan, Peter; Outerbridge, Eugene W.; Aldridge, Andrew; Neims, Allen H.

doi:10.1016/s0022-3476(79)80047-5

Cited by 164 publications

(111 citation statements)

References 20 publications

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“…The mean clearance estimate was 1.8 mL/h/kg, which was lower than the average clearance values (7.9-8.9 mL/h/kg) reported by other studies 20,25,26) . The estimate of the population mean volume of distribution of caffeine (748 mL/kg) is similar to values reported by other studies (911 mL/kg) 2,27) .…”

Section: Discussioncontrasting

confidence: 71%

Clinical Pharmacokinetics of Caffeine in Korean Preterm Infants with Apnea of Prematurity

Lim¹,

Son²,

Shin³

et al. 2017

Neonatal Med

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Purpose: Caffeine shows wide interindividual pharmacokinetic (PK) variation, and therapeutic drug monitoring (TDM) may be needed. The PK profile of caffeine in Korean preterm neonates was investigated, and factors influencing the clearance of caffeine were analyzed. Methods: Fifty-nine preterm neonates receiving caffeine for apnea of prematurity were enrolled in the study (gestational age, 29.5±2.2 weeks and birth weight [BW], 1,318±358 g). Caffeine (20 mg/kg) was intravenously administered to each neonate as a loading dose, followed by a maintenance dose of 5-10 mg/kg/d. A total of 190 serum concentrations were measured for population PK analysis and modeling using nonlinear mixed-effects model (NONMEM ® ) software. Results:The mean serum concentration of caffeine was 15.4±4.5 mg/L (range 7.8-33.0 mg/L). High serum concentrations (>20 mg/L) were noted in 36 samples (29%). At the first measurement of serum caffeine, the mean postmenstrual age was 33.9±2.3 weeks, mean BW was 1,802±471 g, mean duration of treatment was 7.4±9.4 days, and mean sampling time after the last dose was 21.8±2.1 hours. In the population PK analysis, the clearance was 0.033 L/h and volume of distribution was 0.371 L. Typical clearance was calculated as 0.0293×(BW/70) 1.33 . Among the subjects receiving 5 mg/kg/d caffeine, the most significant risk factor associated with high serum concentrations (>20 mg/L) was low BW (P=0.024). Conclusion: BW was the only covariate that influenced caffeine clearance in preterm neonates. Preterm neonates with low BW should be carefully monitored for apnea and adverse reactions in addition to undergoing TDM.

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Section: Discussioncontrasting

confidence: 71%

Clinical Pharmacokinetics of Caffeine in Korean Preterm Infants with Apnea of Prematurity

Lim¹,

Son²,

Shin³

et al. 2017

Neonatal Med

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“…In preterm neonates, the half-life of caffeine ranges from 80 to 100 h (36), which is greater than we observed in fetal sheep. Regardless, fetal sheep were exposed to high levels of caffeine for 15 consecutive days with a peak plasma level of ~30 mg/l/d (equivalent to 154 μmol/l of caffeine).…”

Section: Caffeine and Developing White Mattercontrasting

confidence: 60%

“…We administered caffeine base rather than caffeine citrate to minimize the volume required. Caffeine citrate contains anhydrous citric acid and 50% anhydrous caffeine base; thus, the dose of caffeine base is approximately half that of caffeine citrate (36). On the first 3 d of the caffeine administration (104-106 DG), fetal and maternal arterial pressures were monitored for 1 h before and for 5 h after each daily caffeine administration.…”

Section: Experimental Protocolmentioning

confidence: 99%

Impact of daily high-dose caffeine exposure on developing white matter of the immature ovine brain

et al. 2014

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Background: Caffeine is widely used to treat apnea of prematurity, but the standard dosing regimen is not always sufficient to prevent apnea. Before higher doses of caffeine can be used, their effects on the immature brain need to be carefully evaluated. Our aim was to determine the impact of daily highdose caffeine administration on the developing white matter of the immature ovine brain. Methods: High-dose caffeine (25 mg/kg caffeine base loading dose; 20 mg/kg daily maintenance dose; n = 9) or saline (n = 8) were administered to pregnant sheep from 0.7 to 0.8 of term, equivalent to approximately 27-34 wk in humans. At 0.8 of term, the white and gray matter were assessed histologically and immunohistochemically. results: Daily caffeine administration led to peak caffeine concentration of 32 mg/l in fetal plasma at 1 h, followed by a gradual decline, with no effects on mean arterial pressure and heart rate. Initial caffeine exposure led to transient, mild alkalosis in the fetus but did not alter oxygenation. At necropsy, there was no effect of daily high-dose caffeine on brain weight, oligodendrocyte density, myelination, axonal integrity, microgliosis, astrogliosis, apoptosis, or neuronal density. conclusion: Daily high-dose caffeine administration does not appear to adversely affect the developing white matter at the microstructural level.

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“…The current commonly prescribed dosing regimen for preterm infants with apnea is a loading dose of 10-20 mg/kg caffeine base intravenously or orally, followed by a daily maintenance dose of 2.5-5 mg/kg caffeine base (24). This regimen has proven effective for more than 30 y and is sufficient to prevent or decrease apnea and increase respiratory drive (7). The higher dose used in our study is one that may be used to reduce apnea and facilitate extubation in preterm infants being weaned from mechanical ventilation (25).…”

Section: Caffeine Concentrationmentioning

confidence: 88%

“…Methylxanthines increase central inspiratory drive and minute ventilation; they also improve CO 2 sensitivity, decrease hypoxic depression of breathing, and relax bronchial smooth muscle (4)(5)(6). Caffeine is the methyxanthine that is most commonly used to treat apnea because it has a longer half-life, a higher therapeutic index, and lower toxicity than theophylline (7). Caffeine treatment improves dynamic respiratory compliance during the first week after birth in preterm infants with respiratory distress syndrome (8) and improves diaphragmatic contractility (9,10), both of which improve ventilation and gas exchange.…”

mentioning

confidence: 99%

Effects of caffeine on renal and pulmonary function in preterm newborn lambs

et al. 2012

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IntroductIon: administration of caffeine is associated with a reduction in bronchopulmonary dysplasia, assisted ventilation, patent ductus arteriosus (Da), and cerebral palsy in preterm infants, but the mechanisms are unknown. Our aim was to determine the effects of acute caffeine administration on renal and pulmonary functions in preterm lambs. Methods: Lambs were delivered by cesarean section at ~126 d of gestation and ventilated with a tidal volume of 5 ml/ kg, 60 breaths/min and 5 cmh 2 O positive end-expiratory pressure. after 30 min, lambs received 40 mg/kg caffeine i.v. (n = 7) or saline (controls; n = 6) over 30 min and were ventilated for 2 h. results: arterial concentrations of caffeine reached 35.9 ± 7.8 mg/l. Urine output and mean heart rate were significantly higher after caffeine treatment than in controls (5.86 ± 1.95 vs. 0.76 ± 0.94 ml/kg, area under the curve, P = 0.041 and 211 ± 8 vs. 169 ± 15 beats per minute, P < 0.05, respectively). heart rate remained higher for the experimental period. dIscussIon: caffeine did not affect pulmonary artery or Da blood flows or other renal, respiratory, or cardiovascular parameters examined. Neonatal administration of caffeine increased heart rate and urine output but had little effect on pulmonary function in ventilated preterm lambs.

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Pharmacokinetic profile of caffeine in the premature newborn infant with apnea

Cited by 164 publications

References 20 publications

Clinical Pharmacokinetics of Caffeine in Korean Preterm Infants with Apnea of Prematurity

Clinical Pharmacokinetics of Caffeine in Korean Preterm Infants with Apnea of Prematurity

Impact of daily high-dose caffeine exposure on developing white matter of the immature ovine brain

Effects of caffeine on renal and pulmonary function in preterm newborn lambs

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