Caffeine therapy in preterm infants

Table 1 Pharmacokinetics of caffeine compared to theophylline

	Caffeine	Theophylline
Mechanism of action:
CNS stimulation	More active	Less active
Cardiac stimulation	Less active	More active
Diuresis	Less active	More active
Loading dose	20 to 40 mg/kg per dose IV/PO	4 to 8 mg/kg per dose IV
Maintenance dose	5 to 8 mg/kg per dose once daily IV/PO	1.5 to 3 mg/kg per dose every 8 to 12 h IV
Plasma half-life (h)	40 to 230 (mean, 103)	12 to 64 (mean, 30)
Therapeutic level (mg/L)	5 to 25	7 to 12
Toxic level (mg/L)	> 40 to 50	> 20
Adverse effects:
Cardiovascular	Tachycardia, dysrhythmia	Tachycardia, dysrhythmia
Gastrointestinal	Feeding intolerance, GER	Feeding intolerance, GER
CNS	Jitteriness, irritability, seizures	Jitteriness, irritability, seizures, decreased CBF
Signs of toxicity	Tachycardia, cardiac failure, pulmonary edema, hypertonia, sweating, metabolic disturbances	Tachycardia, agitation, hypokalemia, diuresis, gastric bleeding, seizure
Metabolism	Excreted unchanged or N-demethylation via CYP P450 (CYP1A2) liver-methyltransferase pathway	Excreted unchanged or undergoes 8-hydroxylation via CYP1A2 and CYP2E1
Inter-conversion	3% to 8% converted to theophylline via CYP1A2	25% converted to caffeine via methylation
Routine blood level	Not required	Required
Elimination	86% unchanged in urine	50% unchanged in urine
CSF level	Similar to plasma concentrations	Crosses into the CSF
Clearance (L/kg per hour)[9,43]	0.002 to 0.017	0.02 to 0.05

CNS: Central nervous system; CBF: Cerebral blood flow; CSF: Cerebrospinal fluid; GER: Gastroesophageal reflux; GIT: Gastrointestinal tract.