Pharmacokinetics of midazolam in critically ill pediatric patients.

Midazolam is frequently used to produce sedation in critically ill pediatric patients. We studied the pharmacokinetics of midazolam in 22 patients (age 8 days to 16 years). The intravenous infusion rate to produce sedation ranged from 49-385 mcg/kg/hr.

Drug-nutrient interactions in transplant recipients.

Drug-nutrient interaction refers to an alteration of kinetics or dynamics of a drug or a nutritional element, or a compromise in nutritional status as a result of the addition of a drug. The potentials for drug-nutrient interaction increase with the number of drugs taken by the patient. Organ transplant recipients are therefore at high risk for drug-nutrient interactions because multiple medications are used to manage graft rejection, opportunistic infections, and other associated complications.

The future of hypertension therapy: sense, antisense, or nonsense?

Hypertension is a debilitating disease with significant socioeconomic and emotional impact. Despite recent success in the development of traditional pharmacotherapy for the management of hypertension, the incidence of this disease is on the rise and has reached epidemic proportions by all estimates. This has led many to conclude that traditional pharmacotherapy has reached an intellectual plateau, and novel approaches for the treatment and control of hypertension must be explored.

Effects of COER-verapamil on circadian pattern of forearm vascular resistance and blood pressure.

Controlled-onset extended-release verapamil (COER-V) is designed so drug concentrations rise sharply in the early morning to coincide with the peak incidence of cardiovascular events. The primary objective of this study was to compare the diurnal pattern of forearm vascular resistance (FVR) between hypertensives and normotensives and to determine the effect of COER-V on FVR's diurnal pattern. The authors also studied the effects of COER-V on 24-hour ambulatory blood pressure (ABP) and the early morning blood pressure rise.

Dosage adjustments for antibacterials in obese patients: applying clinical pharmacokinetics.

Obesity is associated with physiological changes that can alter the pharmacokinetic parameters of many drugs. Vancomycin and the aminoglycosides are the only antibacterials that have been extensively investigated in the obese population. The apparent volume of distribution (Vd) and total body clearance of vancomycin are increased in obese patients and have a better correlation with total bodyweight (TBW) than with ideal bodyweight (IBW).

Hypersensitivity or development of antibodies to asparaginase does not impact treatment outcome of childhood acute lymphoblastic leukemia.

Purpose: Development of antibodies and hypersensitivity to asparaginase are common and may attenuate asparaginase effect. Our aim was to determine the relationship between antiasparaginase antibodies or hypersensitivity reactions and event-free survival (EFS).

Patients And Methods: One hundred fifty-four children with acute lymphoblastic leukemia received Escherichia coli asparaginase 10,000 IU/m(2) intramuscularly three times weekly for nine doses during multiagent induction and reinduction phases and for seven monthly doses during continuation treatment.

XK469, a selective topoisomerase IIbeta poison.

XK469 (NSC 697887) is a synthetic quinoxaline phenoxypropionic acid derivative that possesses unusual solid tumor selectivity and activity against multidrug-resistant cancer cells. We report here that XK469 and its S(-) and R(+)-isomers induce reversible protein-DNA crosslinks in mammalian cells. Under protein denaturing conditions, the protein-DNA crosslinks are rendered irreversible and stable to DNA banding by CsCl gradient ultracentrifugation.

Human RNase H-mediated RNA cleavage from DNA-RNA duplexes is inhibited by 6-deoxythioguanosine incorporation into DNA.

Mercaptopurine and thioguanine are anticancer and immunosuppressive agents that exert their primary cytotoxic effects via incorporation of deoxythioguanosine (dG(s)) into DNA, but the precise mechanism(s) by which this causes cytotoxicity remains unknown. We initially determined that the level of dG(s) incorporation into DNA of human T- and B-lineage leukemia cell lines did not correlate significantly with the extent of cytotoxicity (IC(50)), except that there was no cytotoxicity in the absence of dG(s) incorporation. To elucidate biological processes perturbed by dG(s) incorporation into DNA, we chemically synthesized oligodeoxyribonucleotides containing a single dG(s) (11 mer and 19 mer), which decreased the melting temperature (T(m)) of DNA-DNA duplexes without major structural changes, as evidenced by circular dichroism spectra.

Economic impact of digoxin toxicity.

The costs of digoxin toxicity to the US healthcare system have not been previously reported. Therefore, the 1994 database of US University Health-System Consortium (UHC) was searched for cases of digoxin toxicity using the International Classification of Diseases (9th edition) [ICD-9] codes. In addition, the medical records of 17 patients admitted to the University of Illinois Hospital from September 1994 to July 1995 with a diagnosis of digoxin toxicity were also reviewed.

Looking beyond the formulary budget in cost-benefit analysis.

With the introduction of newer, more expensive psychotropic medications, healthcare providers and managed care administrators must consider whether these drugs offer "value for the money." A true picture of the benefits of these drugs emerges only when all the costs of treatment are considered. Focusing exclusively on the acquisition cost of the drug can result in a misleading impression of the drug's worth.

Clinical implications of antidepressant pharmacokinetics and pharmacogenetics.

Objective: To review available data on pharmacokinetic and pharmacogenetic influences on the response to antidepressant therapy, analyze the mechanisms for and clinical significance of pharmacokinetic and pharmacogenetic differences, and explain the implications of pharmacokinetics and pharmacogenetics for patient care.

Data Sources: A MEDLINE search of English-language clinical studies, abstracts, and review articles on antidepressant pharmacokinetics, pharmacogenetics, and drug interactions was used to identify pertinent literature.

Data Synthesis: The pharmacokinetic profiles of selected antidepressants are reviewed and the impact of hepatic microsomal enzymes on antidepressant metabolism is considered.

CYP2D6, N-acetylation, and xanthine oxidase activity in cystic fibrosis.

Study Objective: To determine the activity of CYP2D6, N-acetylation, and xanthine oxidase, three drug-metabolizing enzyme systems, in patients with cystic fibrosis and compare the findings with those in individuals without the disease.

Design: Prospective cohort study.

Setting: General pediatrics service.

Pharmacodynamics of doxorubicin in human bladder tumors.

Intravesical doxorubicin treatment delivers high drug concentrations to the bladder wall, yet the treatment produces only a variable and incomplete response in superficial bladder cancer and insignificant activity in muscle-invading disease. This study evaluated the pharmacological basis for the clinical observations and potential prognostic indicators of tumor sensitivity to doxorubicin. The pharmacodynamics of doxorubicin were studied using histocultures of surgical specimens of seven superficial (Ta and T1) and nine invasive (T2-T4) tumors.

Drug interactions with azithromycin and the macrolides: an overview.

Evidence interactions between individual macrolides and a number of pharmacologically active compounds that are frequently co-administered to patients with bacterial infections is reviewed. Theophylline is strongly associated with erythromycin interaction; clarithromycin may also interact with this drug. Azithromycin, spiramycin and rokitamycin, however, do not appear to have any effect on theophylline pharmacokinetics.

Racial differences in sensitivity to the negative chronotropic effects of propranolol in healthy men.

Objective: Dose-response studies in patients with hypertension have shown that black subjects are less responsive to beta-blocker therapy than white subjects, whereas studies in healthy volunteers suggest marginal or no racial differences in response. No concentration-response studies have been conducted in black subjects and white subjects. The purpose of this study was to characterize beta-blocker pharmacodynamics in healthy black and white men.

Pattern of drug usage in bronchiolitis.

Bronchiolitis is a common viral respiratory infection in infants and young children. The objective of this study was to assess the pattern of drug usage in paediatric patients with bronchiolitis. One hundred patients (aged 2 weeks to 22 months) were evaluated.

Application of chemical immunomodulators to the treatment of cancer and AIDS.

A number of potential advantages, development of promising new agents, and the discovery of synergy with cytokines or cell products continue to spur research into the application of chemical immunomodulators for the treatment of cancer and AIDS. In preclinical in vitro and in vivo systems, chemical immunomodulators definitely modulate the immune system and have therapeutic efficacy. Although clinical trials have shown the ability of these agents to modulate the human immune system, thus far chemical immunomodulators have generally not fulfilled the therapeutic promise generated in animal models for the treatment of human diseases.

Treatment of cryptosporidial diarrhea in an AIDS patient with paromomycin.

Objective: To report a case of diarrhea caused by Cryptosporidium in an AIDS patients which was successfully treated with paromomycin.

Case Summary: An AIDS patient with a 12-month history of cryptosporidial diarrhea unresponsive to other treatment measures was treated with paromomycin 500 mg q6h for 14 days. Before initiating therapy, the patient was experiencing, on average, 20 bowel movements per day and had lost more than 25 kg.

Effects of controlled liver injury and ethanol pretreatment on monoethylglycine xylidide formation in the rat.

Measuring the monoethylglycine xylidide (MEGX) serum level 15-30 min after intravenous administration of lidocaine has been shown to be an accurate predictor of early success in liver transplants. This study evaluates the changes in the MEGX formation test associated with changes in liver mass and ethanol pretreatment in a rat model. Mean MEGX levels were significantly higher for the sham-operated group versus each of the partially hepatectomized groups at 15, 30, and 45 min after injection.

Monitoring cyclic antidepressants.

Therapeutic drug monitoring of antidepressants can ensure that a reasonable amount of drug reached the circulation, can aid in dosage adjustments for treating endogenous depression, can avoid toxicity, and aid in the diagnosis of drug-induced delirium. This article reviews the justification for antidepressant monitoring, discusses sample collection procedures, and presents guidelines for the interpretation of data.

Analgesic plasma concentrations of morphine in children with terminal malignancy receiving a continuous subcutaneous infusion of morphine sulfate to control severe pain.

Three children with terminal malignancy received a continuous subcutaneous infusion of morphine sulfate for the control of severe pain, the morphine dose being adjusted until the patient and/or parent reported complete freedom from pain. Analgesic plasma morphine concentrations at the steady state in these patients ranged from 12.9 to 57 ng/ml (median 19.