Caffeine overdose in a premature infant: Clinical course and pharmacokinetics

The elimination of caffeine was investigated in a 1860g, 31 week gestation neonate, following the accidental administration of a 160 mg.kg(-1) dose. T he first serum concentration measured was 217.5 mg.l(-1) at 36.5 h after do sing. Fitting of time-concentration data was performed using non-linens reg ression with MKMODEL. A first order elimination model was superior to a mix ed order model. Parameter estimates were: clearance 0.01 l.h(-1), volume of distribution 1.17 litres, elimination half-life 81 h, Toxic manifestations included hypertonia, sweating, tachycardia, cardiac failure, pulmonary oed ema and metabolic disturbances (metabolic acidosis, hyper-glycaemia and cre atine kinase elevation), An unusual feature of this infant's illness course was gastric dilatation. These signs resolved by day 7 at a serum concentra tion of 60-70 mg.l(-1). Caffeine clearance has traditionally been reported as either an absolute va lue ol as directly proportional to body weight. The per kilogram model give s an erroneous impression that clearance is greatest in early childhood and then decreases with age until adult rates are reached in late adolescence. Age-related clearance values reported in the literature were reviewed usin g an allometric 3/4 power model. This size model demonstrates that clearanc e increases in infancy and reaches adult rates within the first three month s of life.