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Biomedical subjects

M C Nahata

Publications and source records attributed to M C Nahata.

At least 19 recordsLinked to original sources
PubMed1992

Pharmacokinetics and safety of prochlorperazine in paediatric patients receiving cancer chemotherapy.

Nausea and vomiting are common clinical problems in patients receiving cancer chemotherapy. Metoclopramide is often used but frequently causes extrapyramidal reactions. As an alternative, prochlorperazine is prescribed but no data on its pharmacokinetics in paediatric patients are available to guide the choice of suitable dosages. The primary objective of this study was to evaluate the pharmacokinetics and safety of intravenous prochlorperazine in paediatric patients receiving cancer chemotherapy. Eleven patients (ages 1-9 years) who received high doses of cisplatin or cyclophosphamide were given three to four intermittent doses of 0.2 mg/kg prochlorperazine i.v. over a period of 6-9 h. Multiple blood samples were collected and prochlorperazine was quantified by a specific gas-liquid chromatographic method. The peak serum concentrations ranged from 402 to 5,608 ng/ml. The total clearance and elimination half-life ranged from 0.03 to 0.28 (mean: 0.12) litre/kg/h, and from 1.2 to 15.5 (mean: 5.6) h, respectively. No adverse effects were observed in our patients. Three patients had uncontrolled episodes of vomiting during prochlorperazine therapy. These data suggest: (i) that there was a substantial interpatient variability in prochlorperazine pharmacokinetics thus the dose requirement differed among patients; and (ii) that prochlorperazine appeared safe at the doses used but higher doses may be required to control nausea and vomiting in some paediatric patients receiving high-dose cisplatin or cyclophosphamide therapy.

Adolescent↗
PubMed1992

Advances in paediatric pharmacotherapy.

Marked differences in body composition and organ function development have been demonstrated among neonates, infants, and children versus adults. Specific dosage guidelines for the paediatric population, however, are still not available for the majority of marketed drugs. Much needs to be learned about the pharmacokinetics, pharmacodynamics, comparative efficacy and safety of drugs in infants and children. Recent developments in paediatric therapeutics include the availability of several new antibiotics for the treatment of infections including, streptococcal pharyngitis, otitis media, bacterial meningitis, herpes encephalitis, neonatal herpes, and AIDS. Corticosteroids and intravenous immunoglobulin have become important adjunctive treatments for certain infections. A variety of drugs are available to treat asthma but the mortality due to this disease is still increasing. The identification of a gene defect in patients with cystic fibrosis could lead to more effective treatment in the future. Ondansetron, marketed for use in adults only, shows promise as a more effective and safer antiemetic in children receiving cancer chemotherapy. Numerous drugs are not available in suitable dosage forms for paediatric use and extemporaneous formulations are required. Documentation on the stability of the reformulated drugs is therefore needed. Studies have shown that the methods used for intravenous delivery can influence the serum concentrations of drugs in infants and children. Large numbers of children could be saved worldwide solely with improved vaccination and control of diarrhoea. Despite this, it is encouraging to witness the continued advances being made in paediatric pharmacotherapy.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Recent advances in the treatment of otitis media.

Otitis media (OM) continues to be a major cause of morbidity in infants and children. Antibiotics are presently the mainstay of treatment. A variety of agents including vaccinations against the most common causative organisms, prednisone, non-steroidal anti-inflammatory agents, intravenous immune globulin, antihistamines, decongestants, and topical antibiotics have been investigated. This review will address the recent developments in the treatment and prevention of OM.

Chemotherapy, Adjuvant↗
PubMed1992

Variability in clinical pharmacology of drugs in children.

Numerous factors can lead to variability in pharmacokinetics, pharmacodynamics, efficacy, and toxicity of drugs in infants and children. These may include age, race or genetic status, organ function, underlying disease(s), drug formulation, concomitant drugs, and compliance with therapy. Further research is needed to clarify the mechanisms for variability in drug response to achieve optimal use of drugs in paediatric patients.

Child↗
PubMed1992

The new macrolide antibiotics: azithromycin, clarithromycin, dirithromycin, and roxithromycin.

OBJECTIVE: To review the chemistry, antimicrobial spectrum, pharmacokinetics, clinical trials, adverse effects, and drug interactions of four new macrolide antibiotics: azithromycin, clarithromycin, dirithromycin, and roxithromycin. DATA SOURCES: Information was obtained from comparative clinical trials, abstracts, conference proceedings, and review articles. Indexing terms included azithromycin, clarithromycin, dirithromycin, erythromycin, roxithromycin, and macrolide antibiotics. STUDY SELECTION: Emphasis was placed on comparative clinical trials involving the new macrolide antibiotics. DATA EXTRACTION: Data from human studies published in the English language were evaluated. Trials were assessed by sample size, macrolide dosage regimen, and therapeutic response. DATA SYNTHESIS: The erythromycins have gained widespread use in treating a variety of infections. Although they are effective, limitations include the need to administer four times a day and the intolerable adverse gastrointestinal effects. Four of the more extensively studied agents, azithromycin, clarithromycin, dirithromycin, and roxithromycin, are currently being studied in patients. Based on the studies to date, the newer macrolides may offer several advantages over erythromycin, including: (1) greater antimicrobial activity against certain organisms; (2) longer elimination half-life, thus allowing less frequent administration; and (3) lower incidence of adverse gastrointestinal effects. CONCLUSIONS: The new macrolide antibiotics appear to offer an improvement over erythromycin. Definitive conclusions about the role of these drugs should await completion of ongoing clinical studies.

Anti-Bacterial Agents↗
PubMed1992

Cefotaxime and metabolite disposition in two pediatric continuous ambulatory peritoneal dialysis patients.

OBJECTIVE: To characterize the pharmacokinetics of cefotaxime and desacetylcefotaxime in pediatric patients undergoing continuous ambulatory peritoneal dialysis (CAPD) after intraperitoneal administration of cefotaxime. DESIGN: Case series. SETTING: Ambulatory children from Children's Hospital nephrology clinic, Columbus, Ohio. PATIENT POPULATION: Two adolescents without peritonitis. METHODS: A single intraperitoneal dose of cefotaxime 500 mg per 1 L dianeal was given during CAPD. Cefotaxime and desacetyl-cefotaxime were measured in plasma, urine, and dialysate by HPLC. RESULTS: Maximum plasma concentration (Cmax) of cefotaxime was 11.94 and 13.08 mg/L and that of desacetylcefotaxime 5.73 and 5.33 mg/L. Time to reach maximum concentration (Tmax) of cefotaxime was 2.22 and 4.08 h, and that of desacetylcefotaxime was 5.33 and 5.73 h after instillation of the intraperitoneal cefotaxime dose. Systemic absorption of cefotaxime was 56.6 and 64.8 percent. Total clearance of cefotaxime was 62 and 79 mL/min/1.73 m2. Nonrenal clearance accounted for nearly 95 percent; renal and CAPD clearance contributed approximately 5 percent of the total clearance. Renal and CAPD clearance measurements of desacetylcefotaxime were similar to those for cefotaxime. Cefotaxime half-life was 1.83 and 2.49 h and desacetylcefotaxime half-life was 8.14 and 11.0 h. CONCLUSIONS: Cefotaxime was well absorbed and therapeutic serum concentrations were achieved after intraperitoneal administration. Renal and CAPD clearances for cefotaxime and desacetylcefotaxime were low. Cefotaxime nonrenal clearance was unaffected. Further studies are needed to establish appropriate intraperitoneal dosing guidelines of cefotaxime in pediatric CAPD patients.

Adolescent↗
PubMed1992

Status of child health worldwide.

OBJECTIVE: The objective of this article is to summarize some of the facts about child health and goals of international health organizations. DATA SOURCES: The sources included the publications of World Health Organization's (WHO), United Nations Children Fund, and United Nations Educational, Scientific, and Cultural Organizations; and journal articles. DATA EXTRACTION: Data on areas related to child health were obtained from various publications. DATA SYNTHESIS: Although childhood mortality continues to fall worldwide, nearly 14 million children under five years of age still die annually in developing countries. Diarrhea, measles, tetanus, pertussis, pneumonia, and malnutrition are preventable and treatable and yet account for the majority of deaths. AIDS has begun to substantially affect the pediatric population. It is encouraging that the WHO's goal to immunize 80 percent of all children in the developing world has been met. The World Summit for Children, in consultation with governments of 159 countries, and the agencies of the United Nations, has adopted new goals to be attained by the year 2000. CONCLUSIONS: It is hoped that governmental and nongovernmental agencies will embrace these goals and formulate plans to markedly reduce childhood morbidity and mortality.

Child↗
PubMed1992

Effect of histamine H2-receptor antagonists on vitamin B12 absorption.

OBJECTIVE: To discuss the potential of histamine H2-receptor antagonists (H2RAs) to cause malabsorption of vitamin B12 (cyanocobalamin). DATA SOURCES: Pertinent literature was identified via a MEDLINE search. Journals and references cited in published articles also were used as data sources. STUDY SELECTION: Studies evaluating the effect of H2RAs on vitamin B12 absorption were reviewed. DATA SYNTHESIS: H2RAs decrease acid secretion by the gastric parietal cells. Gastric acid and pepsin produced by these cells are required for the cleavage of vitamin B12 from dietary sources. Intrinsic factor (IF), also produced by gastric parietal cells, is required for vitamin B12 absorption from the gastrointestinal tract. Although H2RAs have not conclusively been shown to decrease IF secretion, studies have demonstrated a significant reduction in food-bound vitamin B12 absorption secondary to decreased acid secretion in patients taking these drugs. CONCLUSIONS: H2RAs have the potential to cause vitamin B12 deficiency. This may be important in patients with inadequate stores of vitamin B12 (e.g., poor diet), particularly those receiving H2RA therapy continuously for more than two years. Healthcare providers should be aware of this potential adverse effect.

Cimetidine↗
PubMed1992

Haemophilus influenzae type B conjugate vaccines.

OBJECTIVE: To review the epidemiology of Haemophilus influenzae type b (Hib) disease, the first Hib vaccine and its limitations, the characteristics and clinical efficacy of the newer conjugate vaccines, and the current recommendations for administration of Hib vaccines. DATA SOURCES: Pertinent literature was identified via a MEDLINE search. Additionally, references cited in published articles were used as data sources. STUDY SELECTION: Studies describing the epidemiology of Hib disease and the efficacy and/or immunogenicity of the Hib vaccines are reviewed. DATA SYNTHESIS: Serious invasive disease secondary to Hib infection causes significant morbidity and mortality in children between the ages of three months and five years. The original Hib vaccine was found to be ineffective in stimulating an adequate immune response in children younger than two years of age. The new Hib conjugate vaccines provide superior efficacy and immunogenicity compared with the original unconjugated vaccine. They stimulate an immune response that is distinctly different from that elicited by the original vaccine. Two vaccine products are currently licensed for use in children as young as two months of age, thus conferring immunity to those children at highest risk for Hib disease. CONCLUSIONS: The new Hib conjugate vaccines provide excellent efficacy and, when used as recommended, may significantly reduce the incidence of invasive Hib disease and its sequelae.

Bacterial Capsules↗
PubMed1992

Stability of ceftazidime (with arginine) stored in plastic syringes at three temperatures.

The stability of ceftazidime (with arginine) stored in plastic syringes at three temperatures was studied. Ceftazidime (with arginine) was reconstituted with sterile water for injection to a concentration of 100 mg/mL and transferred to plastic syringes. Syringes were stored at 22 degrees C for 24 hours; at 4 degrees C for 7 or 10 days, then at 22 degrees C for 24 hours; or at -20 degrees C for 91 days, then at 22 degrees C for 24 hours or at 4 degrees C for seven days followed by 22 degrees C for 24 hours. Ceftazidime concentration was measured at various times by using a stability-indicating high-performance liquid chromatographic method. At each sampling time, each syringe was visually inspected and the pH of each solution was measured. Mean ceftazidime concentration remained > 90% of initial concentration at all storage conditions. Although during storage the color of the solutions changed from light straw to dark yellow and the pH decreased, no precipitate was visually detected and no peaks for degradation products appeared on the chromatograms. Ceftazidime 100 mg/mL (with arginine) in sterile water for injection was stable when stored in plastic syringes for up to 24 hours at 22 degrees C, for 10 days at 4 degrees C followed by up to 24 hours at 22 degrees C, and for 91 days at -20 degrees C followed by up to 24 hours at 22 degrees C or by 7 days at 4 degrees C and up to 24 hours at 22 degrees C.

Arginine↗
PubMed1992

Efficacy of ibuprofen in pediatric patients with fever.

We studied the efficacy of ibuprofen in 56 infants and children (age 0.5-12 years) with rectal temperature greater than or equal to 38.3 degrees C, using a double-blind randomized placebo-controlled design. Ibuprofen liquid was given as a single dose, 5 mg/kg to 18 patients (group I) and 10 mg/kg to 18 patients (group II); placebo was administered to 20 patients (group III). Temperature and vital signs were measured every 0.5-1.0 hours for 8 hours. Multiple blood samples were also collected over this period; ibuprofen plasma concentrations were measured by HPLC. The mean temperature was 38.3 degrees C in group I, 38.1 degrees C in group II, and 38.9 degrees C in group III during 8 hours after drug or placebo administration. The temperature was significantly lower in group I vs III (ibuprofen 5 mg/kg vs placebo) (p less than 0.0005), and group II vs III (ibuprofen 10 mg/kg vs placebo) (p less than 0.0001). The temperature was also markedly different for patients in group I vs II (ibuprofen 5 mg/kg vs ibuprofen 10 mg/kg) between 4 and 8 hours after the dose (p less than 0.01). The duration of action was longer for ibuprofen 10 mg/kg than 5 mg/kg. The mean maximum decrease from baseline temperature was 1.3 degrees C, 1.8 degrees C and 0.8 degrees C for group I, II and III, respectively. The maximum reduction in temperature occurred at 3-4 hours in the ibuprofen groups, and at 7 hours in the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Temperature↗
PubMed1991

Pharmacokinetics of ibuprofen in febrile children.

Ibuprofen may be an alternative to acetaminophen to control fever in children but little is known about its pharmacokinetics in pediatric patients. We studied 17 patients (age 3-10 yr) with fever; the most prevalent diagnoses were streptococcal pharyngitis and otitis media. Ibuprofen liquid was given as a single dose, 5 mg/kg (9 patients) or 10 mg/kg (8 patients). Multiple blood samples were collected over 8 hours and analyzed by HPLC. The maximum observed serum concentrations of ibuprofen ranged from 17-42 micrograms.ml-1 at 5 mg.kg-1 and 25-53 micrograms.ml-1 at 10 mg.kg-1 doses. Pharmacokinetics did not appear to be affected by ibuprofen dose. Mean tmax, oral clearance and elimination half life were 1.1 h, 1.2 ml.min-1.kg-1, and 1.6 h, respectively in patients at 5 mg.kg-1 doses; the corresponding values were 1.2 h, 1.4 ml.min-1.kg-1, and 1.6 h in those receiving 10 mg.kg-1 doses. There was no relationship between age and ibuprofen kinetics. No adverse effects occurred in any patients. These data suggest that ibuprofen pharmacokinetics may not be affected by dose between 5 and 10 mg/kg or age between 3 and 10 years.

Administration, Oral↗
PubMed1991

Dopamine pharmacokinetics in critically ill newborn infants.

Dopamine is frequently used in critically ill newborn infants for treatment of shock and cardiac failure, but its pharmacokinetics has not been evaluated using a specific analytical method. Steady-state arterial plasma concentrations of dopamine were measured in 11 seriously ill infants receiving dopamine infusion, 5-20 micrograms.kg-1.min-1, for presumed or proven sepsis and hypotensive shock. Steady-state concentrations of dopamine ranged from 0.013-0.3 microgram/ml. Total body clearance averaged 115 ml.kg-1.min-1. The apparent volume of distribution and elimination half life averaged 1.8 l.kg-1 and 6.9 min, respectively. No relationship was observed between dopamine pharmacokinetics and gestational age, postnatal age or birthweight. Substantial interindividual variation was seen in dopamine pharmacokinetics in seriously ill infants, and plasma concentrations could not be predicted accurately from its infusion rate. Marked variation in clearance explains in part, the wide dose requirements of dopamine needed to elicit clinical response in critically ill newborn infants.

Birth Weight↗
PubMed1991

Prolonged sedation associated with secobarbital in newborn infants receiving ventilatory support.

Newborn infants receiving ventilatory support often require sedation. Secobarbital is commonly used in these patients, but dosage guidelines to avoid prolonged sedation are not available. Seventeen infants (gestational age, 30 to 40 weeks; postnatal age, 0 to 3 days) with hyaline membrane disease or persistent pulmonary hypertension on mechanical ventilation were studied. These patients received secobarbital, 4 to 14 mg/kg/day intravenously for 1 to 10 days to produce sedation. Sedation was considered prolonged if it lasted more than 24 hours after the last dose. Nine of 17 infants experienced prolonged sedation. The mean daily secobarbital dose was 11.2 mg/kg/day in patients with prolonged sedation and 6.9 mg/kg/day in those patients without (p less than 0.05); the cumulative mean dose in the respective groups was 33.3 and 21.3 mg/kg (p less than 0.05). Four infants were sedated for 3 to 4 days after stopping secobarbital; the mean daily and cumulative dose was 13 mg/kg/day and 53 mg/kg in these patients. Duration of sedation was related to both daily and cumulative doses of secobarbital. Based on our results, the daily dose of secobarbital should not exceed 7 mg/kg/day to avoid prolonged sedation in infants. Frequent monitoring appears necessary to ensure efficacy with the lowest cumulative dose of secobarbital in newborn infants.

Humans↗
PubMed1991

Plasma concentrations of morphine in children with chronic pain--comparison of controlled release and regular morphine sulphate tablets.

Comparative plasma concentrations of morphine in two children with chronic pain who received controlled-release and regular morphine sulphate tablets are described. The controlled-release tablets were given every 12 h and regular tablets every 4 h. At steady-state, the maximum morphine plasma concentration (Cmax) was 24.1 ng/ml at 45 mg and 18.7 ng/ml at 30 mg of controlled-release morphine sulphate tablets. The Cmax was 17.6 ng/ml at 15 mg and 31.4 ng/ml at 20 mg dose of the regular tablets. The maximum concentration occurred at 2.0 and 2.5 h after controlled-release and 0.25 and 1.5 h after regular tablets. The minimum morphine plasma concentrations and the area under the plasma concentration-time curve normalized for dose were comparable for the controlled-release and regular tablets. These data indicate that controlled-release morphine sulphate may be well absorbed in relation to the regular tablets. If these results are confirmed in a large group of patients, the controlled-release morphine sulphate tablets may offer a convenient (less frequent) dosing compared with regular tablets in children suffering from chronic pain due to malignancy.

Child↗