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J V Aranda

Publications and source records attributed to J V Aranda.

At least 109 records · Page 6Linked to original sources
PubMed1979

Caffeine metabolism in the newborn.

The concentrations of caffeine and metabolites in urine have been examined as a function of age to explore the remarkably slow elimination of caffeine by human infants. Urine samples were obtained from 3 adults and 10 infants aged 8 days to 8 months during therapeutic treatment with caffeine. A high-performance liquid chromatographic (HPLC) procedure involving reversed-phase partition chromatography was developed to separate caffeine and 13 of its metabolites. During the first month of life, caffeine accounted for more than 85% of the identifiable products in urine. Caffeine remained the predominant component for the first 3 months, but its percentage decreased gradually to the adult value of less than 2% by the age of 7 to 9 months. This change reflected increasing metabolite production, not decreasing urinary caffeine concentration. The adult metabolite pattern of partially demethylated xanthines and urates was attained by 7 to 9 months. The data indicate that the 4-day plasma t1/2 of caffeine characteristic of the newborn depends in large part on slow urinary excretion of unchanged drug since there is little or no metabolism. Subsequent decrease in the t1/2 to about 4 hr by the age of 8 months correlates closely with the rise in metabolite production.

Adult↗
PubMed1979

Pharmacokinetic profile of caffeine in the premature newborn infant with apnea.

The pharmacokinetic profile of caffeine was studied in 32 premature newborn infants with apnea: 12 following a single intravenous dose; 3 after a single oral dose; 7 during treatment with an initial empirical (high) maintenance dose schedule; and 10 during treatment with a revised (lower) dose schedule. Mean (+/- SE) AV d, t 1/2, ke1, and clearance following a single intravenous dose were 0.916 +/- 0.070 1/kg, 102.9 +/- 17.9 hours, 0.009 +/- 0.001/hours and 8.9 +/- 1.5 ml/kg/hour, respectively. Rapid absorption was noted with plasma concentrations of 6 to 10 mg/l achieved within 30 minutes to two hours following an oral dose of 10 mg/kg. Cpss of caffeine in infants given a high empirical dose (11.2 +/- 1.5 mg/kg/day) ranged from 22.5 to 84.2 mg/l (mean = 45.3) whereas a dose schedule based on kinetic data (2.5 mg/kg/day) yielded plasma concentrations ranging from 7.4 to 19.4 mg/l (mean = 13.7). We suggest a loading dose of 10 mg/kg intravenously or orally followed by a daily maintenance dose of 2.5 mg/kg/day administered as a single dose for the treatment and prevention of neonatal apnea.

Administration, Oral↗
PubMed1979

Metabolism of theophylline to caffeine in premature newborn infants.

Plasma concentrations of theophylline and caffeine in seven premature neonates receiving theophylline orally for treatment of apnea at age one to 9 days were measured by high performance liquid chromatography, ultraviolet spectrophotometry, and mass spectrometry. Plasma concentrations of caffeine increased from 1.8 mg/l (range = 0.1 to 3.7) at day one to 3.7 mg/l (1.3 to 8.0) seven days after initiation of theophylline therapy. Similarly, plasma concentrations of theophylline were 4.6 mg/l (1.5 to 7.5) and 11.0 mg/l (4.0 to 19.0) on days one and 7 of theophylline therapy, respectively. In contrast, four normal adult volunteers given theophylline orally for eight to ten days had plasma theophylline concentrations ranging from 3 to 14 mg/l but no measurable caffeine. This indicates that caffeine is a biotransformation product of theophylline in premature neonates and that the metabolic pathway followed by theophylline in premature infants includes a methylation reaction producing caffeine, whereas in adults, the major metabolic pathway involves oxidative reactions (demethylation and oxidation). Some pharmacologic effects attributed to theophylline during chronic therapy for apnea may in part be due to caffeine. Routine monitoring during theophylline therapy in premature neonates with apnea should include plasma concentrations of both theophylline and caffeine in order to assess the total methylxanthine load.

Adult↗
PubMed1979

Sequelae of caffeine treatment in preterm infants with apnea.

Growth, neurologic, and ophthalmologic assessments were done in 21 low-birth-weight infants given caffeine for neonatal apnea and in 21 matched control infants. Caffeine significantly decreased the need for and the duration of mechanical ventilation. No difference in growth and development was noted between the control and caffeine-treated infants. A high incidence of cicatricial retrolental fibroplasia was observed in both control (10/21) and caffeine-treated infants (7/18).

Apnea↗
PubMed1979

Maturation of caffeine elimination in infancy.

The developmental changes in caffeine elimination were studied in 7 infants aged between 2 1/2 weeks and 6 months. Adult plasma clearance rate of caffeine was achieved at 3 to 4 1/2 months of age. Plasma half-life and elimination rate reached adult levels after 3 to 4 1/2 months and seemed to exceed adult capacity thereafter. No significant changes in apparent volume of distribution were noted. Our data provide some indication of the age in infancy when the low rates of caffeine elimination in the neonate increase to the adult rate.

Adult↗
PubMed1979

Methylxanthines in apnea of prematurity.

Caffeine and theophylline are effective in the treatment of apnea in the newborn infant. Controlled studies of efficacy and comparative efficacy and studies of toxicity are visibly lacking. Both drugs exert their anti-apneic activity by stimulation of the respiratory center. Both drugs are eliminated from the baby slowly (caffeine even slower than theophylline) and doses should be adjusted accordingly. Neonates excrete caffeine largely unchanged and they methylate theophylline to caffeine significantly. Caffeine seems preferable to theophylline because of its wider therapeutic index, ease of administration (i.e., given once per day), lesser fluctuation in plasma concentration owing to longer half-life, potent central respirogenic effect, and fewer peripheral side effects. Areas of concern and feasible research have been discussed.

Apnea↗
PubMed1978

Pharmacokinetic disposition and protein binding of furosemide in newborn infants.

Using a one-compartment model, the pharmacokinetic disposition of furosemide was studied in eight premature and term neonates with fluid overload. Following a single intravenous injection of furosemide (1 to 1.5 mg/kg), multiple blood samples were obtained from a heelstick or an arterial catheter and analyzed for furosemide by gas liquid chromatography. The mean (+/- SE) apparent volume of distribution was 829.2 +/- 118.9 ml/kg; t1/2 was 7.7 +/- 1.0 hour; elimination rate constant was 0.102 +/- 0.013/hour and plasma clearance was 81.61 +/- 14.98 ml/kg/hour. Compared to the disposition of furosemide in normal adults. AVd is almost fourfold greater in the neonate with an eightfold prolongation in plasma t1/2, an eightfold decrease in Ke1, and a twofold decrease in plasma clearance. Neither gestational and postnatal age nor birth weight correlated with the pharmacokinetic variables. No significant change in reserve bilirubin-binding capacity after an intravenous dose of furosemide was noted. Slow elimination of furosemide may partly explain the prolonged diuretic and saluretic effect of furosemide in the neonate.

Bilirubin↗
PubMed1977

Efficacy of caffeine in treatment of apnea in the low-birth-weight infant.

The efficacy of caffeine citrate in the management of apnea in the newborn infant was evaluated. Caffeine citrate was given to 18 preterm neonates with recurrent apneic spells. Mean (+/- SE) birth weight and gestational age were 1,065.0 +/- 71.9 gm and 27.5 +/- 0.6 weeks, respectively. Mean age at onset of apnea and at initiation of caffeine treatment was 6.5 +/- 3.7 days and 18.2 +/- 4.9 days, respectively. Caffeine citrate was administered with a loading dose of 20 mg/kg intravenously followed within two to three days by 5 to 10 mg/kg once or twice daily. All infants except one showed a significant decrease in the frequency of apneic episodes associated with caffeine therapy. Mean frequencies of apneic spells were 13.6 +/- 2.5 and 2.1 +/- 0.6 apnea per day before and after initiation of caffeine treatment, respectively. Respiratory rate was increased, and blood [h]+ion concentration and Pco2 were decreased. The data suggest that caffeine is an effective pharmacologic respirogenic agent in the preterm infant with apnea.

Apnea↗
PubMed1977

Pharmacokinetic observations of phenytoin disposition in the newborn and young infant.

The pharmacokinetic profile of phenytoin (DPH) was studied in 30 infants aged 2 days to 96 weeks. The plasma DPH half-life during the first week of life in term infants was prolonged and very variable (20-7 +/- 11-6 h, mean +/-SD). Thereafter the plasma half-life was much shorter (7-6 +/- 3-5 h). In preterm infants the half-life was much longer (75-4 +/- 64-5 h) and more variable. The mean apparent volume of distribution was similar in these groups of infants: preterm newborn 0-80 +/- 0-22 l/kg, term infants during the first week of life 0-80 +/- 0-26 l/kg, and term infants greater than 2 weeks of age 0-73 +/- 0-18 l/kg. Predictions of steady-state plasma DPH concentrations, based on these kinetic parameters, were confirmed. Very low "trough" plasma DPH concentrations were observed after the 14th postnatal day in 19 infants receiving 8 mg/kg per 24 h orally. On the other hand, infants of less than one week of age receiving the same dose, especially if preterm, frequently showed drug accumulation to toxic plasma DPH concentrations. The impaired binding of DPH to newborn plasma protein was confirmed but "normal adult values" were approached by the age of 3 months. An intravenous loading dose of 8 mg/kg (sodium phenytoin) can be expected to generate a mean plasma DPH concentration of 10 mg/l (40 micronmol/l) in the newborn. Loading doses of up to 12 mg/kg were given without untoward effects. During the first week or so of life plasma Dph half-life is so variable that no fixed dosage regimen can be derived from the available data. Beyond the second week of life, however, a dose of 8 mg/kg per 24 h is probably inadequate for most infants.

Half-Life↗
PubMed1977

Alterations in blood pressure during exchange transfusion.

Blood pressure changes as a function of the rates of blood withdrawal and infusion were determined during exchange blood transfusion in 2 preterm newborn infants. 10 ml blood withdrawal and infusion completed within 3 minutes resulted in reversible changes in aortic pressure, whereas the same procedure completed within 45 to 60 seconds resulted in a progressive fall in the systolic pressure and in narrowing of the pulse pressure. In one of the cases this was associated with respiratory arrest. An exchange rate of 5 ml/kg per 3 minutes is recommended.

Blood Pressure↗
PubMed1976

Pharmacokinetic aspects of theophylline in premature newborns.

To characterize further the pharmacokinetics of theophylline in premature infants, its concentraion in blood was measured by high-pressure liquid chromatography after intravenous infusion given to six apneic premature newborns three to 15 days of age. Theophylline's apparent volume of distribution was 0.690 +/- 0.095 liters per kilogram (mean +/- S.E.), a value similar to that of children, but the half-life (30.2 +/- 6.5 hours) was nine times longer. Blood clearance rate (17.6 +/- 2.3 ml per kilogram per hour) was lower than plasma clearance rate (100 ml per kilogram per hour) of young children. At a total plasma concentration of 17 mg per liter, 56.4 +/- 3.8 and 36.4 +/- 3.8 per cent of the theophylline was bound to adult or full-term cord plasma proteins, respectively. Bilirubin and theophylline did not compete for plasma protein. Calculations suggest that a loading doses of 5.5 mg per kilogram and a maintenance dose rate of 1.1 mg per kilogram per eight hours would achieve and maintain a mean blood concentration of 8 mg per liter (about 10 mg per liter in plasma).

Adult↗