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At least 109 records · Page 6Linked to original sources
PubMed1993

Decreased acetylation of isoniazid in chronic renal failure.

Pharmacokinetic parameters of isoniazid obtained from 37 normal subjects were compared with parameters obtained from 14 patients with chronic renal failure. In the 29 normal rapid acetylators and eight normal slow acetylators, the mean plasma half-life values of isoniazid were 1.54 +/- 0.31 and 3.68 +/- 0.59 hours, respectively. The plasma half-life values of isoniazid in patients with chronic renal failure varied widely from 1.30 to 10.13 hours, but the values were significantly longer than those of normal subjects. Because isoniazid clearance is governed mainly by hepatic metabolism, such a significant prolongation of plasma half-life of isoniazid was unexpected; thus the pharmacokinetics of isoniazid were reevaluated in the same patients with chronic renal failure after the kidney transplantation. After successful kidney transplantation, the shortening of isoniazid half-life was pronounced and the nonrenal clearance was markedly increased. These findings indicate that decreased isoniazid clearance in chronic renal failure is caused in minor part by the decreased renal excretion of isoniazid and in major part by the depressed hepatic N-acetylation of isoniazid.

Acetylation↗
PubMed1991

Salmonella typhimurium (TA100) mutagenicity of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone and its open- and closed-ring analogs.

The mutagenicities of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX, compound 1), 3-chloro-4-(dichloromethyl)-2(5H)-furanone (RMX, compound 6), and 2-(dichloromethyl)-3,3-dichloropropenal (TCB, compound 7) were determined in the same assay and in repetitive determinations using Salmonella typhimurium (TA 100) without microsomal fraction activation. In addition, the mutagenicity of 2-methyl-3,3-dichloropropenal (compound 8) was assayed in the same manner although not simultaneously with MX, RMX, and TCB. This study was undertaken to ascertain the role of open- and closed-ring forms of MX in the mutagenicity of MX. MX proved to be roughly 100 times more mutagenic than the open-ring analogue TCB and 10 times more mutagenic than the closed-ring analogue RMX. Compound 8 was inactive. Assay stability of the three active compounds in Vogel-Bonner medium at 38 degrees C was estimated as the chemical half-life values by following the change in UV absorbance at selected wave lengths. Half-life values were 10.7, 2.6, and 2.8 hr, respectively, for MX, RMX, and TCB. The enhanced mutagenicity of MX relative to RMX and TCB is attributed to the intrinsic mutagenicity of MX and its greater stability is judged to play only a minor role. Moreover, the greater mutagenicity of the closed-ring analogue RMX relative to the open-ring analogue TCB points to the ring form of MX as the active species even though the open form of MX is predominant under assay conditions.

Drug Stability↗
PubMed1999

Mizolastine: antihistaminic activity from preclinical data to clinical evaluation.

Mizolastine, a new H1-receptor antagonist, is highly selective for histamine H1 receptors and has no anticholinergic, antiadrenergic, or antiserotonin activity. It is rapidly absorbed after oral ingestion, with peak plasma concentrations occurring at 1.5 h. The distribution and terminal elimination half-life values are 2 and 13 h, respectively, in healthy young adult volunteers. Half-life values are longer in the elderly and in subjects with chronic renal insufficiency; however, the differences are not large enough to be clinically relevant or to necessitate a dose adjustment in these populations. Mizolastine produces prompt, sustained, peripheral blockade of histamine H1 receptors in the skin. Suppression of the histamine-induced wheal and flare begins 40-60 min after ingestion of a 10-mg dose, peaks at 3-4 h, lasts for at least 24 h, and does not decrease during regular once-daily dosing. The amount of wheal suppression is comparable to that produced by other leading new H1-receptor antagonists. These pharmacokinetic and pharmacodynamic studies of mizolastine provide its clinical pharmacology 'signature'. They also provide the scientific rationale for recommending a once-daily 10-mg dose and suggest that the efficacy and effectiveness of mizolastine will be widely confirmed in allergic disorders, especially rhinitis and urticaria.

Adult↗
PubMed2003

The value of life according to "law as a way to survive".

Law as a Way to Survive is a comprehensive evolution-theory orientated philosophy of law and state that is tested in this article on its pertinence and explanatory power for the following issues: animal rights, abortion, euthanasia and assisted suicide. These subjects are suitable as tests precisely because they are not those for which LWS or rival theories, with which it will be compared, and for which it was primarily developed for. It will be concluded that LWS is very superior in pertinence and explanatory power both because it is much less metaphysical and much more complex than its rivals.

Abortion, Induced↗
PubMed1995

Age and gender related changes in stereoselective pharmacokinetics and pharmacodynamics of verapamil and norverapamil.

1. Pharmacokinetics and pharmacodynamics of R- and S-verapamil and R- and S-norverapamil were studied at steady state following administration of 180 mg verapamil delivered by a controlled-release gastrointestinal therapeutic system (COER-verapamil). 2. Of the 30 young (19 to 43 years) and 30 elderly subjects (65 to 80 years) enrolled, approximately half of each age group were women; all subjects were healthy and none were smokers. 3. Mean R- and S-verapamil and R- and S-norverapamil Cmax, Cmin, and AUC values for elderly subjects were 1.2 to 2.2 times greater than those for young subjects; these differences were statistically significant at P < 0.05. Median tmax values for young and elderly subjects were not significantly different for any enantiomer. The mean half-life values of R- and S-verapamil for elderly subjects were approximately 20 h compared with approximately 13 h for young subjects, respectively. The mean half-life values of R- and S-norverapamil for elderly subjects were approximately 31 h and 20 h, respectively, compared with approximately 19 h and 21 h for young subjects, respectively. 4. In both age groups, the mean plasma verapamil concentrations of each enantiomer were higher for women than for men at all time points. 5. Mean arterial pressure (MAP) had a significant correlation to R- (r2 = 0.86) and S-verapamil (r2 = 0.87) concentration values that was not influenced by either gender or age of the patient. Change in PR-interval also had a significant correlation to R- and S-verapamil concentration values. However, the sensitivity of the response to changes in R- and S-verapamil concentration values in elderly subjects was about 1/5 of that in younger subjects.

Adult↗
PubMed2004

Adrenoceptor agonist poisoning after accidental oral ingestion of brimonidine eye drops.

OBJECTIVE: Brimonidine tartrate is a relatively selective alpha(2) adrenic agonist that lowers elevated intraocular pressure. A 2-yr-old boy presented with severe cardiorespiratory symptoms of systemic alpha(2) adrenergic intoxication after accidentally ingesting 2 mL of brimonidine ophthalmic solution (0.2%) orally. At 20 mins after ingestion, he became acutely pale and lethargic, with shallow infrequent respirations. The symptoms resolved completely within the next 10 hrs. METHODS: The pharmacokinetics of brimonidine in plasma and urine were analyzed using gas chromatography and mass spectrometry. RESULTS: Maximum plasma concentrations were 40 ng/mL 5 hrs after ingestion. The plasma elimination half-life value was 2.7 hrs. Elimination via urine was calculated as having a terminal half-life value of 3.2 hrs. CONCLUSIONS: This case illustrates the ability of brimonidine to gain rapid access to the central nervous system. This first passage is followed by a redistribution phase with rising plasma concentrations. Children who accidentally ingest brimonidine orally should be admitted to a pediatric intensive care unit.

Administration, Oral↗
PubMed1986

[Comparative studies of the metabolism of MCT/LCT and LCT emulsions in diabetics].

In 7 moderately overweight non-insulin dependent diabetics with slightly elevated triglyceride levels, disappearance rates of MCT/LCT- und LCT-emulsions were compared. 5 metabolically healthy volunteers served as control. During a 3-hour lipid infusion, serum triglycerides reached a steady state with both emulsions in the healthy controls, whereas in diabetic patients, steady state triglyceride levels were seen only with MCT/LCT. After the end of the lipid infusion, the longest half life value concerning the decline of triglyceride levels was found with LCT in diabetics, while significantly shorter and quite similar half life values were found with LCT in healthy controls and MCT/LCT in diabetics. The shortest half life for serum triglycerides was expectedly found in healthy controls. According to these data, parenteral nutrition with lipids in states of disturbed glucose and lipid metabolism--if necessary--should preferentially be done with MCT/LCT emulsions.

Diabetes Mellitus, Type 2↗
PubMed1991

Half-lives of 214Pb and 214Bi.

New measurements on chemically separated samples of 214Bi have yielded a mean half-life value of 19.71 +/- 0.02 min, where the error quoted is twice the standard deviation of the mean based on 23 decay runs. This result provides strong support for the historic 19.72 +/- 0.04 min half-life value and essentially excludes the 19.9-min value, both reported in previous studies. New measurements of the decay rate of 222Rn progeny activity initially in radioactive equilibrium have yielded a value of 26.89 +/- 0.03 min for the half-life of 214Pb, where the error quoted is twice the standard deviation of the mean based on 12 decay runs. This value is 0.1 min longer than the currently accepted 214Pb half-value of 26.8 min.

Bismuth↗
PubMedDate not supplied

Comparison of metabolic clearance rates of MCT/LCT and LCT emulsions in diabetics.

In seven moderately overweight noninsulin-dependent diabetics with slightly elevated triglyceride levels, disappearance rates of infused medium chain triglyceride/long chain triglyceride (MCT/LCT) and long chain triglyceride (LCT) emulsions were compared. Five metabolically healthy volunteers served as controls. During a 3-hr lipid infusion, serum triglycerides reached a steady state with both emulsions in the healthy controls, whereas, in diabetic patients, steady state triglyceride levels were seen only with MCT/LCT. After the end of the lipid infusion, the longest half-life value in the decline of triglyceride levels was found with LCT in diabetics, whereas significantly shorter and quite similar half-life values were found with LCT in healthy controls and with MCT/LCT in diabetics. As expected, the shortest half-life for serum triglycerides was found in healthy controls after MCT/LCT-infusion. Virtually the same differences in serum concentrations and in half-life times were seen with free fatty acids. According to these data, if needed, parenteral nutrition with lipids in states of disturbed glucose and lipid metabolism may preferentially be done with MCT/LCT emulsions.

Blood Glucose↗
PubMed1987

Allylic compounds bind directly to DNA: investigation of the binding mechanisms in vitro.

The in vitro binding of three allyl compounds, allyl methanesulphonate, allyl bromide and allyl chloride to DNA from salmon sperm was investigated. Kinetic DNA-alkylation measurements revealed significant differences between the strongly alkylating allyl methanesulphonate and allyl bromide with half-life values of 1.5 h and 8.1 h, respectively and the weakly alkylating allyl chloride with a half-life value of 360 h. Five alkylated nucleic bases, 3-allyladenine, N6-allyladenine, N2-allylguanine, 7-allylguanine and O6-allylguanine, could be identified after DNA-alkylation with all three allyl compounds.

Alkylating Agents↗
PubMedDate not supplied

Comparative pharmacokinetics of amikacin following a single intramuscular or subcutaneous administration in goats (Capra hircus).

The pharmacokinetics of amikacin sulfate was investigated following a single intramuscular (i.m.) or subcutaneous (s.c.) administration (10 mg/kg). The plasma concentration versus time data were analysed using the biexponential equation for first-order absorption and elimination phases for both the i.m. and s.c. routes. The absorption half life values for the i.m. and s.c. routes were found to be 14.64 and 12.36 min, respectively. The biological half-life values of amikacin following i.m. and s.c. routes were found to be 84.46 and 93.96 min, respectively. The systemic availability of amikacin for both the i.m. (102.15 +/- 5.08%) and s.c. (106.82 +/- 12.95%) routes was found to be almost complete. Thus, based on the data of short absorption half life, almost complete systemic availability, slightly longer biological half life and ease of administration, we suggest that the s.c. route be preferred over the i.m. route for amikacin administration in goats. Amikacin at a dose level of 8 mg/kg body weight at 12 h intervals would result in a therapeutic peak plasma concentration (Cpmax) of 32.30 micrograms/mL, which is not expected to produce any oto- or nephropathic effects.

Absorption↗
PubMed1988

A steady-state study on the formation of Compounds II and III of myeloperoxidase.

The reaction between native myeloperoxidase and hydrogen peroxide, yielding Compound II, was investigated using the stopped-flow technique. The pH dependence of the apparent second-order rate constant showed the existence of a protonatable group on the enzyme with a pKa of 4.9. This group is ascribed to the distal histidine imidazole, which must be deprotonated to enable the reaction of Compound I with hydrogen peroxidase to take place. The rate constant for the formation of Compound II by hydrogen peroxide was 3.5.10(4) M-1.s-1. During the reaction of myeloperoxidase with H2O2, rapid reduction of added cytochrome c was observed. This reduction was inhibitable by superoxide dismutase, and this demonstrates that superoxide anion radicals are generated. When potassium ferrocyanide was used as an electron donor to generate Compound II from Compound I, the pH dependence of the apparent second-order rate constant indicated involvement of a group with a pKa of 4.5. However, with ferrocyanide as an electron donor, protonation of the group was necessary to enable the reaction to take place. The rate constant for the generation of Compound II by ferrocyanide was 1.6.10(7) M-1.s-1. We also investigated the reaction of Compound II with hydrogen peroxide, yielding Compound III. Formation of Compound III (k = 50 M-1.s-1) proceeded via two different pathways, one of which was inhibitable by tetranitromethane. We further investigated the stability of Compound II and Compound III as a function of pH, ionic strength and enzyme concentration. The half-life values of both Compound II and Compound III were independent of the enzyme concentration and ionic strength. The half-life value of Compound III was pH-dependent, showing a decreasing stability with increasing pH, whereas the stability of Compound II was independent of pH over the range 3-11.

Algorithms↗
PubMed1997

Sustained stress and fixed interval performance.

The effects of sustained stress on response rate and temporal patterning (quarter-life) of rats performing either a previously learned fixed-interval schedule (FI 60) or learning an FI 60 simultaneously with stress onset were determined. Rats lived 24 h/day in operant cages, where they earned all of their food via lever-pressing. During the stress portion of each experiment, one group of rats was able to avoid or escape signalled intermittent footshock (Avoidance/ Escape Group), a second group (Yoked) did not have control over shock termination, a third group never received shock (Control). Shock trials were presented around the clock at approximately 5-min intervals and the stress portion of each study lasted 1-2 weeks. We have previously reported that rats tolerate this paradigm well and avoid/escape 99% of the shock trials. In rats previously trained on the FI task, both rate of responding and quarter-life values were significantly decreased on the first day of stress for both the Avoidance/Escape and Yoked Groups. Food intakes and quarter-life values were not significantly different from the controls by stress Days 3 and 2, respectively. In the acquisition study, controls learned the F1 task by Day 4 as judged by quarter-life of responding. FI task acquisition was significantly impaired in stressed rats compared to controls, not reaching asymptotic performance until Day 9 of stress. There were no major differences between the 2 stress groups in either study. These data demonstrate that stress may impair both the rate and patterning of behavior, and suggest that this rodent paradigm may usefully model some aspects of the effects of stress in humans.

Animals↗
PubMed1977

Clinical pharmacology of methicillin in neonates.

The pharmacokinetic properties of methicillin were investigated in 59 newborn infants. Concentrations of methicillin in serum were approximately 58 and 80 microng/ml at one hour after 25 and 50 mg/kg doses, respectively. The average serum half-life values ranged from one to three hours and were inversely correlated with birth weight and chronologic age. The half-life values, volumes of distribution, and plasma clearances of methicillin are shown in relationship to gestational age and chronologic age. A dosage of 25 mg/kg is recommended for therapy of most neonatal staphylococcal diseases; the frequency of administration is altered on the basis of birth weight and chronologic age.

Birth Weight↗
PubMed1998

Pharmacodynamics of (-)-beta-2',3'-dideoxy-3'-thiacytidine in chronically virus-infected woodchucks compared to its pharmacodynamics in humans.

The pharmacodynamics of (-)-beta-2',3'-dideoxy-3'-thiacytidine (3TC) was studied in chronically woodchuck hepatitis virus-infected woodchucks and compared to that in previous studies in hepatitis B virus (HBV)-infected humans. Net depletion rates of serum virus DNA in woodchucks receiving 3TC were modeled as a sum of an exponentially declining virus input and a first-order elimination. Preceding shoulders and pseudo-first-order virus half-lives in serum ranged from 1 to 7 days and were dose dependent. Higher plasma 3TC concentrations were needed in woodchucks for virus depletion similar to that attained in humans. Human HBV depletion curves from a previous clinical study with 3TC (>/=100 mg per day) were described by a biexponential relationship. The average half-life value in humans, normalized to fraction of area under the serum virus load-time curve, was similar to the average half-life value observed in woodchucks given the highest 3TC dose (2.4 and 2.0 days, respectively). On cessation of therapy, virus load rebounds in woodchucks were dose dependent and resembled posttherapy virus "flares" reported to occur in humans. The estimates of drug exposures that could lead to optimal antiviral effects presented indicate that 3TC should not be underdosed and compliance should be monitored. The study of chronically infected woodchucks may prove useful for optimizing drug regimens for hepadnavirus infections.

Animals↗
PubMed1988

Predictive value of life events, psychosocial factors and self-rated health on disability in an elderly rural French population.

Increasing evidence suggests that exposure to stressful life events and a variety of psychosocial factors are related to different health outcomes in the elderly. Our purpose is to study the predictive value of each of these items on the ability deterioration of a panel of 645 rural adults, aged 60 and over, living at home and followed for 4 years (1982-1986). This survey was carried out in five rural areas of Haute-Garonne (South-West France). Data were collected from the elderly themselves by questionnaire in 1982 and 1986. An indicator of ability evolution (1982-1986) was constructed for all those surviving and reviewed in 1986. Our study concerned 470 elderly people. Ability deterioration was 55.3% (260 elderly people). The analysis of age-adjusted relative risks (RR) of ability deterioration showed a significant impact of economic level (RR = 2.3), self-rated health (RR = 2.2) and reported morbidity (RR = 2.2). Among the psychosocial factors, we noted the predictive role of a lack of project for the future (RR = 1.7) and mostly of a feeling of uselessness (RR = 9.8), but also of non-participation in association activities for people aged less than 75. All these relationships remain significant after adjustment according to reported morbidity. In contrast, no significant effect was found for social support and life events which occurred during the follow-up period. Logistic discriminant analysis and segmentation analysis were performed. They confirmed the independence of the predictive roles played by age, economic level, reported morbidity and the feeling of uselessness. These results, discussed with bibliographic data, should give a better knowledge of the processes which underlie pathological ageing.

Activities of Daily Living↗