Biomedical subjects

J D Rogers

Publications and source records attributed to J D Rogers.

At least 37 records · Page 2Linked to original sources

PubMed2000

Montelukast adult (10-mg film-coated tablet) and pediatric (5-mg chewable tablet) dose selections.

Montelukast is a selective leukotriene receptor antagonist that has been shown to be effective in the treatment of chronic asthma. It is approved in more than 70 countries for patients 6 years of age and older. For adults (> or = 15 years of age), a 10-mg film-coated tablet (FCT) is available, and for children (aged 6 to 14 years), a 5-mg chewable tablet (CT) is available. The adult montelukast dose (10-mg FCT) was selected on the basis of classic dose-ranging studies as the lowest dose that produces maximal improvement in both measures of airway function and patient-reported outcomes in chronic asthma and in the attenuation of exercise-induced bronchoconstriction. The strategy used for the pediatric dose selection for montelukast was based on the determination of a CT dose that would provide an overall systemic exposure to montelukast in children similar to that in adults who receive a 10-mg FCT dose. Because montelukast was to be given chronically for the treatment of asthma, the area under the plasma concentration-time curve was considered to be the pharmacokinetic measurement that best represented systemic exposure to the drug. A 5-mg CT yielded a comparable single-dose area under the plasma concentration-time curve profile to that of the adult 10-mg FCT dose and, therefore, was selected as the pediatric dose for children aged 6 to 14 years with asthma. Subsequently, 2 studies of efficacy and tolerability validated the choice of the 5-mg CT dose.

Acetates↗

PubMed2000

A 10-year national trend study of alcohol consumption, 1984-1995: is the period of declining drinking over?

OBJECTIVES: Data from the 1984, 1990, and 1995 National Alcohol Surveys were used to investigate whether declines shown previously in drinking and heavy drinking across many demographic subgroups have continued. METHODS: Three alcohol consumption indicators--current drinking (vs abstaining), weekly drinking, and weekly heavy drinking (5 or more drinks in a day)--were assessed for the total US population and for demographic subgroups. RESULTS: Rates of current drinking, weekly drinking, and frequent heavy drinking, previously reported to have decreased between the 1984 and 1990 surveys, remained unchanged between 1990 and 1995. Separate analyses for each beverage type (beer, wine, and spirits) and most demographic subgroups revealed similar temporal patterns. CONCLUSIONS: Alcohol consumption levels, declining since the early 1980s, may reach a minimum by the 21st century. Consumption levels should be monitored carefully over the next few years in the event that long-term alcohol consumption trends may be shifting.

Adult↗

PubMed2000

Disposition and pharmacokinetics of the antimigraine drug, rizatriptan, in humans.

The absorption and disposition of rizatriptan (MK-0462, Maxalt(TM)), a selective 5-HT(1B/1D) receptor agonist used in the treatment of migraine headaches, was investigated in humans. In a two-period, single i.v. (3 mg, 30-min infusion), and single oral (10 mg) dose study with [(14)C]rizatriptan in six healthy human males, total recovery of radioactivity was approximately 94%, with unchanged rizatriptan and its metabolites being excreted mainly in the urine (89% i.v. dose, 82% p.o. dose). Approximately 26 and 14% of i.v. and oral rizatriptan doses, respectively, were excreted in urine as intact parent drug. In a second, high-dose study (60 mg p.o.), five metabolites excreted into urine were identified using liquid chromatography-tandem mass spectrometry and NMR methods. They were triazolomethyl-indole-3-acetic acid, rizatriptan-N(10)-oxide, 6-hydroxy-rizatriptan, 6-hydroxy-rizatriptan sulfate, and N(10)-monodesmethyl-rizatriptan. Urinary excretion of triazolomethyl-indole-3-acetic acid after i.v. and oral administrations of rizatriptan accounted for 35 and 51% of the dose, respectively, whereas the corresponding values for rizatriptan-N(10)-oxide were 4 and 2% of the dose. Plasma clearance (CL) and renal clearance (CL(r)) were 1325 and 349 ml/min, respectively, after i.v. administration. A similar CL(r) value was obtained after oral administration (396 ml/min). The primary route of rizatriptan elimination occurred via nonrenal route(s) (i.e., metabolism) because the CL(r) of rizatriptan accounted for 25% of total CL. Furthermore, the CL(r) was higher than normal glomerular filtration rate ( approximately 130 ml/min), indicating that this compound was actively secreted by renal tubules. The absorption of rizatriptan was approximately 90%, but it experienced a moderate first-pass effect, resulting in a bioavailability estimate of 47%.

Administration, Oral↗

PubMed2000

Electroconvulsive therapy for elderly patients with multiple system atrophy: a case series.

Multiple system atrophy (MSA) is a progressive neurological illness associated with parkinsonism. Electroconvulsive therapy (ECT) improves motor function in Parkinson's disease and, thus, might be beneficial in MSA. Three cases of MSA treated with ECT are described. All patients improved neurologically, but none regained independent ambulation. A review, including previously reported cases, demonstrates that ECT can be safe and effective for depression associated with MSA. Reduced tremor and rigidity may occur, but substantial gait improvement cannot be expected.

Activities of Daily Living↗

PubMed2000

Simvastatin does not affect CYP3A activity, quantified by the erythromycin breath test and oral midazolam pharmacokinetics, in healthy male subjects.

Potential for inhibition of CYP3A activity by simvastatin, an HMG-CoA reductase inhibitor, was evaluated in 12 healthy male subjects who received placebo or 80 mg of simvastatin, the maximal recommended dose, once daily for 7 consecutive days. On day 7, an intravenous injection of 3 microCi [14C N-methyl]erythromycin for the erythromycin breath test (EBT) was coadministered with a 2 mg oral solution of midazolam. The values for percent 14C exhaled during the first hour (for EBT) and the pharmacokinetic parameters of midazolam (AUC, Cmax, t1/2) were not affected following multiple once-daily oral doses of simvastatin 80 mg. The 95% confidence interval was 0.97 to 1.18 for EBT and 0.99 to 1.23 for midazolam AUC. In addition, the total urinary recoveries of midazolam and its 1'-hydroxy metabolites (free plus conjugate) obtained from both treatments were not statistically different (p > 0.200). These data demonstrate that multiple dosing of simvastatin, at the highest recommended clinical dose, does not significantly alter the in vivo hepatic or intestinal CYP3A4/5 activity as measured by the commonly used EBT and oral midazolam probes.

Administration, Oral↗

PubMed1999

Falling asleep at the wheel: motor vehicle mishaps in persons taking pramipexole and ropinirole.

The authors report a new side effect of the dopamine agonists pramipexole and ropinirole: sudden irresistible attacks of sleep. Eight PD patients taking pramipexole and one taking ropinirole fell asleep while driving, causing accidents. Five experienced no warning before falling asleep. The attacks ceased when the drugs were stopped. Neurologists who prescribe these drugs and patients who take them should be aware of this possible side effect.

Aged↗

PubMed1999

Determination of L-753,037 in human plasma by liquid chromatography/turbo ionspray tandem mass spectrometry.

A liquid chromatographic/turbo ionspray tandem mass spectrometric (LC/MS/MS) method was developed and validated for the determination of L-753,037, a potent endothelin receptor antagonist currently under development for the treatment of cardiovascular diseases, in human plasma. L-753,037 is extracted from 0.5 ml of human plasma using liquid-liquid extraction and analyzed by LC/MS/MS with a turbo ionspray interface. Method validation results showed that this method is very sensitive, reliable, selective and reproducible. L-753,048, an ethoxy analogue of L-753,037, was used as the internal standard. The method has a lower limit of quantitation (LOQ) of 50 pg ml(-1) with a linear calibration range of 0.05-50 ng ml(-1). The intra-day precision and accuracy (n = 5) were measured to be below 10% relative standard deviation (RSD) and between 97.4 and 102.8% of the nominal values, respectively, for all calibration standard concentrations within the calibration curve range. The inter-day precision and accuracy (n = 3 days, 5 replicates per day) were measured to be below 6.5% RSD and between 99.3 and 102.0% of the nominal values, respectively, for all quality control concentrations. The extraction recovery was determined to be approximately 99% on average. The analyte was found to be stable in plasma through three freeze-thaw cycles, for at least 4 h at ambient temperature and for up to 40 days under -20 degrees C freezer storage conditions. The analyte was also shown to be stable for at least 24 h in the reconstitution solution at room temperature and for up to 3 days as a dried extract at 4 degrees C. Additional variations in plasma concentration of the analyte due to the use of different sources of plasma were also evaluated.

Calibration↗

PubMed1999

Update on the incidence and mortality from melanoma in the United States.

BACKGROUND: Increases in the incidence of malignant melanoma have been among the largest of all cancers in the United States. OBJECTIVE: We report updated trends in melanoma rates among the US white population. METHODS: Incidence and mortality rates were calculated for 1973 to 1994. Trends were examined with stratification by state, age, and sex, and by anatomic site, stage, and melanoma thickness at diagnosis. RESULTS: Melanoma incidence and mortality rates increased dramatically from 1973 to 1994, rising 120.5% and 38.9%, respectively. In recent years, however, rates for most age-sex groups appeared to stabilize or even decline. Male patients continued to have higher incidence and mortality rates than female patients, but for both male and female patients the largest increases by site were for the trunk. A large proportion of melanomas were detected in the local stage and with a thickness less than 0.75 mm. CONCLUSION: Prevention of sun exposure is recommended to reverse the high incidence rates of melanoma.

Adult↗

PubMed1999

Alcoholic beverage choice, risk perception and self-reported drunk driving: effects of measurement on risk analysis.

AIMS: The present study examined effects of measurement on risk curve analysis in an application involving prediction of frequency and indicator measures of drunk driving with beverage-specific alcohol consumption and risk perception measures. DESIGN AND PARTICIPANTS: From a 1995 in-person survey of the US adult household population (response rate = 77%) the responses of 1260 adult drivers who reported any drinking in the prior year were selected for analysis. Regression and graphical techniques were used to investigate relationships between drinking pattern, beverage choice, perception of risks of drinking before driving, and frequency of drunk driving. MEASUREMENTS: Self-reported drunk driving (occurrence) was measured by a question assessing driving after drinking enough to be in trouble if stopped by the police within the prior 12 months; those affirming this (n = 191) were asked how many times they did so (frequency). Alcohol consumption was assessed by beverage and in combination. Risk perception was assessed as a factor score from three correlated measures. Demographic variables included age, ethnicity, education and income. FINDINGS: Controlling for demographics, heavy beer consumption (p < 0.01) more than heavy wine (NS) or liquor/spirits (p < 0.05) intake was strongly predictive of risk perception. A regression analysis showed a significant interaction between heavy beer consumption and perceived risk (p < 0.001) in predicting reported frequency of drunk driving, after controlling for heavy beer consumption (p < 0.05), total alcohol consumption and risk perception (both ps < 0.001). No interactions were important in equivalent models predicting dichotomous occurrence. Graphic analysis showed the shape of the risk curve is altered when frequency of drunk driving is taken into account rather than simple occurrence. CONCLUSIONS: Individuals' underestimation of beer's intoxicating effects, compared to other alcoholic beverage types, helps explain beer's over-representation in drinking driving violation reports. There is a need for creative public health campaigns designed to inform young men of beer's alcohol content and associated risks.

Adult↗

PubMed1999

Pharmacokinetics and tolerability of oral rizatriptan in healthy male and female volunteers.

AIMS: The pharmacokinetics and dose proportionality of rizatriptan single oral doses from 2.5 to 15 mg administered as solutions to healthy volunteers were studied. METHODS: In a randomized, crossover study with four periods, twenty-four healthy volunteers (12 males and 12 females) took single oral doses of 2.5, 5, 10, and 15 mg rizatriptan in Periods 1-4. In a fifth period, subjects received 4 mg intravenous (i.v.) rizatriptan as a reference. Plasma and urine rizatriptan concentrations were determined at several timepoints/intervals for 12 and 24 h, respectively. RESULTS: The arithmetic mean AUC values following single oral doses of 2.5, 5, 10, and 15-mg rizatriptan were 16, 33, 72, and 127 ng ml-1 h, respectively, in males; and 19, 42, 97, and 161 ng ml-1 h, respectively, in females. The overall bioavailability (F ) of rizatriptan was approximately 40% in males. Following the 4 mg reference i.v. dose, the apparent plasma clearance (CL) and renal clearance (CLr ) were 1042 and 225 ml min-1, respectively, in males; and 821 and 174 ml min-1, respectively, in females. CONCLUSIONS: The disposition kinetics of oral rizatriptan were linear for doses of 2. 5-10 mg in males, and for doses of 2.5-5 mg in females. However, the degree of nonlinearity for higher doses was minor for both genders. The plasma concentrations of rizatriptan were slightly greater in women compared to men but the difference was not considered to be clinically meaningful. Also, the clearance of rizatriptan appeared to be mainly nonrenal.

Administration, Oral↗

PubMed1999

Grapefruit juice has minimal effects on plasma concentrations of lovastatin-derived 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors.

OBJECTIVE: To evaluate the effect of regular-strength grapefruit juice, a cytochrome P4503A4 (CYP3A4) inhibitor, on the pharmacokinetics of a commonly prescribed regimen of oral lovastatin. METHODS: In a randomized crossover study, 16 healthy subjects received a single 40 mg dose of lovastatin in the evening after each consumed an 8-ounce glass of regular-strength grapefruit juice or water with breakfast for 3 consecutive days. The effect of the same grapefruit juice and water regimen on the pharmacokinetics of midazolam (2 mg oral dose given 1 hour after the third day of grapefruit juice and water) was used as a positive control in the same subjects. Plasma concentrations of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors were determined by an enzyme inhibition assay, and concentrations of lovastatin, lovastatin acid, and midazolam were determined by liquid chromatography-tandem mass spectrometry. RESULTS: The area under the plasma concentration-time profiles (AUC) and maximum plasma concentrations (Cmax) of HMG-CoA reductase inhibitors increased slightly (-30% for each) after consumption of grapefruit juice. Similar effects on AUC and Cmax (approximately 40% increase for each) were noted after analysis of samples of hydrolyzed plasma (which converts inactive lactones to active hydroxy acid species). The AUC and Cmax values for lovastatin approximately doubled in the presence of grapefruit juice, whereas the same parameters for lovastatin acid increased 1.6-fold. Grapefruit juice caused the AUC for midazolam to increase by a factor of approximately 2.4. CONCLUSIONS: Daily consumption of a glass of regular-strength grapefruit juice has a minimal effect on plasma concentrations of HMG-CoA reductase inhibitors (approximately 30% to 40% increase) after a 40 mg evening dose of lovastatin.

Adult↗

PubMed1999

Prevalence of the amylase-binding protein A gene (abpA) in oral streptococci.

Salivary amylase binds specifically to a number of oral streptococcal species. This interaction may play an important role in dental plaque formation. Recently, a 585-bp gene was cloned and sequenced from Streptococcus gordonii Challis encoding a 20.5-kDa amylase-binding protein (AbpA). The goal of this study was to determine if related genes are present in other species of oral streptococci. Biotinylated abpA was used in Southern blot analysis to screen genomic DNA from several strains representing eight species of oral streptococci. This probe hybridized with a 4.0-kb HindIII restriction fragment from all 13 strains of S. gordonii tested. The probe did not appear to bind to any restriction fragments from other species of amylase-binding oral streptococci including Streptococcus mitis (with the exception of 1 of 14 strains), Streptococcus crista (3 strains), Streptococcus anginosus (1 strain), and Streptococcus parasanguinis (1 strain), or to non-amylase-binding oral streptococci including Streptococcus sanguinis (3 strains), Streptococcus oralis (4 strains), and Streptococcus mutans (1 strain). Primers homologous to sequences within the 3' and 5' ends of abpA yielded products of 400 bp following PCR of genomic DNA from the Southern blot-positive strains. Several of these PCR products were cloned and sequenced. The levels of similarity of these cloned products to the abpA of S. gordonii Challis ranged from 91 to 96%. These studies reveal that the abpA gene appears to be specific to S. gordonii and differs from genes encoding amylase-binding proteins from other species of amylase-binding streptococci.

Amylases↗

PubMed1999

Montelukast dose selection in 6- to 14-year-olds: comparison of single-dose pharmacokinetics in children and adults.

Montelukast, an oral leukotriene-receptor antagonist, has demonstrated efficacy and tolerability for the treatment of chronic asthma in adults. A once-daily 10 mg dose (film-coated tablet) was selected as the optimal adult dose based on dose-ranging studies. Asthma is a similar disease and is treated with the same medications in children and adults. These observations suggested that a dose of montelukast in children providing overall drug exposure (i.e., montelukast plasma concentrations) similar to that of the 10 mg film-coated tablet dose in adults would be efficacious, well tolerated, and obviate the need for separate dose-ranging studies in children. Therefore, the dose of montelukast for 6- to 14-year-old children was selected by identifying the chewable tablet dose of montelukast yielding a single-dose area under the plasma concentration-time curve (AUC) comparable to that achieved with the adult 10 mg film-coated tablet dose. Based on this approach, which included dose normalization of data from several pediatric pharmacokinetic studies, a 5 mg chewable tablet dose of montelukast was selected for use in clinical efficacy studies in 6- to 14-year-old children with asthma.

Acetates↗

PubMed1999

Beer drinking accounts for most of the hazardous alcohol consumption reported in the United States.

OBJECTIVE: Patterns and correlates of hazardous drinking, defined as occasions in which five or more drinks were consumed in a day, were compared for wine, beer and distilled spirits. METHOD: From a probability sample of the U.S. adult household population, 2,817 respondents who had consumed at least one drink in the previous year were selected for analysis. RESULTS: The results show that, in the U.S., beer accounts for the bulk of alcohol consumed by the heaviest drinkers. Beer also accounts for a disproportionate share of hazardous drinking. Logistic regression analyses revealed that drinkers who consume beer in a hazardous fashion at least monthly are more likely to be young, male and unmarried, and less likely to be black than are other drinkers. Hazardous beer consumption is more predictive of alcohol-related problems than hazardous consumption of wine or spirits. CONCLUSIONS: Three potential explanations for the results are considered: advertising, beer-drinking subcultures and risk compensation. Additional research is urged in order to better specify the causal role of these and other factors in hazardous beer drinking.

Adult↗

PubMed1999

Who drinks most of the alcohol in the US? The policy implications.

OBJECTIVE: The concentration of alcohol consumption in the U.S. among the heaviest drinkers is analyzed with data from two recent probability samples of the adult population. METHOD: Pooled data from four national telephone surveys (N = 7,049; 4,784 drinkers) with uniform methodology are used for the primary analysis, and data from an in-person national household survey (N = 2,058; 1,308 drinkers) are used for confirmatory analysis. Each survey systematically measured self-reported alcohol consumption during the prior year using a "graduated frequencies" approach designed to capture drinking at a series of amount-per-day levels. RESULTS: The two studies produced very similar estimates: the top 2.5% of drinkers by volume account for 27% and 25% of the nation's total self-reported alcohol consumption in the telephone and in-person surveys, respectively; the top 5% account for 42% and 39%; and the top 20% of drinkers account for 89% and 87% in each survey, respectively. Men were overrepresented at the highest volumes, contributing about 76% of the country's total reported consumption. Similarly, young adults aged 18 to 29 are disproportionately represented in the heaviest drinking levels; constituting 27% of the population, they account for about 45% of overall adult drinking. CONCLUSIONS: The bulk of the alcohol reported drunk in the U.S. is consumed by a relatively small population of very heavy drinkers. Prevention policies implied by this concentration include strengthening of social norms discouraging heavy consumption, restricting marketing practices that target heavy drinkers, and implementing measures to reduce consumption by the heaviest drinkers.

Adult↗

PubMed1999

Sun protection behaviors among African Americans.

The anatomic distribution of some skin cancers suggests that sun exposure may be an etiologic factor for skin cancer among African Americans. Yet little is known about sun protection behaviors among African Americans. We analyzed data from the 1992 National Health Interview Survey (N = 1,583) to determine the prevalence of sun protection behaviors and sun sensitivity. About 6% of African Americans reported being extremely sensitive to the sun and severe sunburning, and 9% reported mild burns. Overall, 53% of respondents (47% of men and 57% of women) reported that they were very likely to wear protective clothing, seek shade, or use sunscreen lotion. Women were more likely than men to report seeking shade and using sunscreen. Sun protection behaviors were more frequently reported by those who sunburn more easily and were positively associated with age. Use of sunscreen was positively associated with income and education. Education about sun protection and early detection may help reduce the morbidity and mortality of skin cancer among African Americans.

Adolescent↗

PubMed1998

High-performance liquid chromatographic methods for the determination of a new carbapenem antibiotic, L-749,345, in human plasma and urine.

A column-switching, reversed-phase high-performance liquid chromatographic (HPLC) method for the determination of a new carbapenem antibiotic assay using ultraviolet detection has been developed for a new carbapenem antibiotic L-749,345 in human plasma and urine. A plasma sample is centrifuged and then injected onto an extraction column using 25 mM phosphate buffer, pH 6.5. After 3 min, using a column-switching valve, the analyte is back-flushed with 10.5% methanol-phosphate buffer for 3 min onto a Hypersil 5 microm C18 BDS 100x4.6 mm analytical column and then detected by absorbance at 300 nm. The sample preparation and HPLC conditions for the urine assay are similar, except for a longer analytical column 150x4.6 mm. The plasma assay is specific and linear from 0.125 to 50 microg/ml; the urine assay is linear from 1.25 to 100 microg/ml.

Anti-Infective Agents↗

PubMed1998

Determination of pilocarpic acid in human plasma by capillary gas chromatography with mass-selective detection.

A novel, highly sensitive method for the determination of pilocarpic acid (PA) in human plasma is described. In addition, the method provides for the conversion of the lactone, pilocarpine (P), to PA so that a total drug presence can be determined. Using novel high-performance liquid chromatographic conditions capable of separating P, isopilocarpine (I-P), PA and isopilocarpic acid (I-PA) from each other and from endogenous plasma impurities, it was confirmed that P exclusively and quantitatively converts to PA in heparinized human plasma during storage. For the determination of PA, the selective extraction of PA from protein-free plasma was accomplished using two different solid-phase extraction (SPE) cartridges in two consecutive SPE steps. After extraction, PA was lactonized with trifluoroacetic acid back to P, and both P and an internal standard were acylated using heptafluorobutyric anhydride (HFBA). The trifluoroacetylated derivatives were monitored using gas chromatography (GC) with mass spectrometric (MS) detection. This procedure allowed the sensitive and reliable determination of PA with a limit of quantification (LOQ) of 1 ng/ml, which could not be achieved using previously described methods. The assay was validated in the concentration range of 1 to 10 ng/ml with an intra-day precision (expressed as the coefficient of variation, C.V.) ranging from 9.9 to 0.5%. Inter-day precision for the quality control standard at 2.5 ng/ml showed a C.V. of 10.2%. Accuracy ranged from 94 to 102%. The assay was used to monitor the maximum systemic exposure to P, administered by the ocular route, in terms of total plasma PA (P and PA).

Gas Chromatography-Mass Spectrometry↗