Metronidazole Elimination is Preserved in the Elderly

1990 ◽  
Vol 9 (3) ◽  
pp. 155-159 ◽  
Author(s):  
Steffen Loft ◽  
Charlotte Egsmose ◽  
Jesper Sonne ◽  
Henrik Enghusen Poulsen ◽  
Martin Døssing ◽  
...  
Keyword(s):  
Old Age ◽  
Half Life ◽  
Renal Excretion ◽  
The Elderly ◽  
Volume Of Distribution ◽  
Time Curve ◽  
Concentration Time ◽  
Age Related ◽  
Young Subjects ◽  
Hydroxy Metabolite

1 The disposition of metronidazole and its major metabolites was compared in 11 subjects aged 86 ± 6 years and 8 aged 30 ± 6 years. 2 The plasma clearance of metronidazole was 1.20 ± 0.53 and 1.25 ± 0.22 ml min-1 kg -1, the volume of distribution 0.77 ± 0.27 and 0.77 ± 0.09 1 kg -1 and the half-life 7.8 ± 1.9 and 7.2 ± 0.9 h in elderly and young subjects, respectively (P > 0.05). 3 The area under the plasma concentration-time curve of the hydroxy metabolite was 32 ± 14 and 21 ± 3 mM min-1 (P < 0.05) whereas its half-life was 21 ± 14 and 12 ± 2 h (P < 0.05) in the elderly and young subjects, respectively. 4 The recovery in the urine of metronidazole and its metabolites was 42 ± 21% and 87 ± 6% of dose in elderly and young subjects, respectively (P < 0.05). With this reservation the only elimination pathways of metronidazole affected by old age were the renal excretion of unchanged compound and the hydroxy metabolite. 5 It is concluded that the ability to eliminate metronidazole is preserved in old age and that age-related dose adjustments are not necessary.

scholarly journals Safety, toleration, and pharmacokinetics of intravenous azithromycin.

1996 ◽  
Vol 40 (11) ◽  
pp. 2577-2581 ◽  
Author(s):  
D R Luke ◽  
G Foulds ◽  
S F Cohen ◽  
B Levy
Keyword(s):  
Half Life ◽  
Active Drug ◽  
Slow Release ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Time Curve ◽  
Concentration Time ◽  
Elimination Half ◽  
The Mean ◽  
Male Subjects

To date, the clinical pharmacology of large intravenous doses of azithromycin has not been described. In the present study, single 2-h intravenous infusions of 1, 2, and 4 g of azithromycin were administered to three parallel groups (in each group, six received active drug and two received placebo) of healthy male subjects. Toleration (assessed by scores of subject-administered visual analog scale tests spanning 0 [good] to 10 [poor]), safety, pharmacokinetics, and serum motilin levels were monitored for up to 240 h after the start of each intravenous infusion. Mean nausea scores of 0.0, 0.0, 1.0, and 0.5 and abdominal cramping scores of 0.0, 0.0, 0.4, and 0.4 for 12-h periods after doses of 0, 1, 2, and 4 g of azithromycin, respectively, suggested that azithromycin was well tolerated. Because of the standardized 1-mg/ml infusates, all subjects in the 4-g dosing group complained of an urgent need to urinate. There were no consistent trends in endogenous motilin levels throughout the study. The maximum concentration of azithromycin in serum (10 micrograms/ml after a 4-g dose) and the area under the concentration-time curve (82 micrograms.h/ml after a 4-g dose) were dose related. The mean pharmacokinetic parameters were an elimination half-life of 69 h, total systemic clearance of 10 ml/min/kg, and a volume of distribution at steady state of 33.3 liters/kg. The pharmacokinetic results suggest that the long half-life of azithromycin is due to extensive uptake and slow release of the drug from tissues rather than an inability to clear the drug. Single intravenous doses of up to 4 g of azithromycin in healthy subjects are generally well tolerated, and quantifiable concentrations may persist in serum for 10 days or more.

scholarly journals Pharmacokinetics of a Fluoronaphthyridone, Trovafloxacin (CP 99,219), in Infants and Children following Administration of a Single Intravenous Dose of Alatrofloxacin

2000 ◽  
Vol 44 (5) ◽  
pp. 1195-1199 ◽  
Author(s):  
John S. Bradley ◽  
Gregory L. Kearns ◽  
Michael D. Reed ◽  
Edmund V. Capparelli ◽  
John Vincent
Keyword(s):  
Volume Of Distribution ◽  
Intravenous Dose ◽  
Pharmacokinetic Parameters ◽  
Single Intravenous Dose ◽  
Average Standard Deviation ◽  
Time Curve ◽  
Concentration Time ◽  
Age Related ◽  
The Mean ◽  
In Infants And Children

ABSTRACT The pharmacokinetics of trovafloxacin following administration of a single intravenous dose of alatrofloxacin, equivalent to 4 mg of trovafloxacin per kg of body weight, were determined in 6 infants (ages 3 to 12 months) and 14 children (ages, 2 to 12 years). There was rapid conversion of alatrofloxacin to trovafloxacin, with an average ± standard deviation (SD) peak trovafloxacin concentration determined at the end of the infusion of 4.3 ± 1.4 μg/ml. The primary pharmacokinetic parameters (average ± SD) analyzed were volume of distribution at steady state (1.6 ± 0.6 liters/kg), clearance (151 ± 82 ml/h/kg), and half-life (9.8 ± 2.9 h). The drug was well tolerated by all children. There were no age-related differences in any of the pharmacokinetic parameters studied. Less than 5% of the administered dose was excreted in the urine over 24 h. On the basis of the mean area under the concentration-time curve of 30.5 ± 10.1 μg · h/ml and the susceptibility (≤0.5 μg/ml) of common pediatric bacterial pathogens to trovafloxacin, dosing of 4 mg/kg/day once or twice daily should be appropriate.

Comparison of Pharmacokinetics and Pharmacodynamics of Docetaxel and Cisplatin in Elderly and Non-Elderly Patients: Why Is Toxicity Increased in Elderly Patients?

2004 ◽  
Vol 22 (14) ◽  
pp. 2901-2908 ◽  
Author(s):  
Hironobu Minami ◽  
Yuichi Ohe ◽  
Seiji Niho ◽  
Koichi Goto ◽  
Hironobu Ohmatsu ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Phase Ii ◽  
The Elderly ◽  
Volume Of Distribution ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Two Phase ◽  
Time Curve ◽  
Concentration Time ◽  
Phase Ii Studies ◽  
The Difference

PurposeFollowing phase I studies of docetaxel and cisplatin in patients with non–small-cell lung cancer, the recommended doses of docetaxel were different for elderly (≥ 75 years) and non-elderly (< 75 years) patients. To elucidate the mechanism of the difference, the pharmacokinetics of docetaxel and cisplatin were investigated in two phase II studies separately conducted in elderly and non-elderly patients.Patients and MethodsTwenty-seven elderly and 25 non-elderly patients were treated with three weekly administrations of docetaxel and cisplatin every 4 weeks. Doses of docetaxel were 20 and 35 mg/m2for elderly and non-elderly patients, respectively. All patients received 25 mg/m2of cisplatin. The pharmacokinetics and pharmacodynamics of docetaxel and cisplatin were compared in elderly and non-elderly patients.ResultsThere were no differences in pharmacokinetics of docetaxel or cisplatin between elderly versus non-elderly patients with regard to clearance and volume of distribution. In the pharmacodynamic analysis, neutropenia was positively correlated with the area under the concentration-time curve for docetaxel but not for cisplatin. In evaluating the relationship between neutropenia and the area under the concentration-time curve of docetaxel, elderly patients experienced greater neutropenia than those predicted by a pharmacodynamic model developed in non-elderly patients; the residual for prediction of the percent change in neutrophil count was −11.2% (95% CI, −21.8 to −0.5%).ConclusionThe pharmacokinetics of docetaxel and unchanged cisplatin were not different between elderly and non-elderly patients. The elderly patients were more sensitive to docetaxel exposure than the non-elderly patients, resulting in the different recommended doses for the phase II studies.

scholarly journals Pharmacokinetics and Distribution over the Blood-Brain Barrier of Zalcitabine (2′,3′-Dideoxycytidine) and BEA005 (2′,3′-Dideoxy-3′-Hydroxymethylcytidine) in Rats, Studied by Microdialysis

1998 ◽  
Vol 42 (9) ◽  
pp. 2174-2177 ◽  
Author(s):  
Natalia Borg ◽  
Lars Ståhle
Keyword(s):  
Protein Binding ◽  
Half Life ◽  
Extracellular Fluid ◽  
Volume Of Distribution ◽  
Time Curve ◽  
Concentration Time ◽  
Water Partition Coefficient ◽  
The Mean ◽  
The Brain

ABSTRACT Microdialysis was applied to sample the unbound drug concentration in the extracellular fluid in brain and muscle of rats given zalcitabine (2′,3′-dideoxycytidine; n = 4) or BEA005 (2′,3′-dideoxy-3′-hydroxymethylcytidine; n = 4) (50 mg/kg of body weight given subcutaneously). Zalcitabine and BEA005 were analyzed by high-pressure liquid chromatography with UV detection. The maximum concentration of zalcitabine in the dialysate (C max) was 31.4 ± 5.1 μM (mean ± standard error of the mean) for the brain and 238.3 ± 48.1 μM for muscle. The time to C max was found to be from 30 to 45 min for the brain and from 15 to 30 min for muscle. Zalcitabine was eliminated from the brain and muscle with half-lives 1.28 ± 0.64 and 0.85 ± 0.13 h, respectively. The ratio of the area under the concentration-time curve (AUC) (from 0 to 180 min) for the brain and the AUC for muscle (AUC ratio) was 0.191 ± 0.037. The concentrations of BEA005 attained in the brain and muscle were lower than those of zalcitabine, withC maxs of 5.7 ± 1.4 μM in the brain and 61.3 ± 12.0 μM in the muscle. The peak concentration in the brain was attained 50 to 70 min after injection, and that in muscle was achieved 30 to 50 min after injection. The half-lives of BEA005 in the brain and muscle were 5.51 ± 1.45 and 0.64 ± 0.06 h, respectively. The AUC ratio (from 0 to 180 min) between brain and muscle was 0.162 ± 0.026. The log octanol/water partition coefficients were found to be −1.19 ± 0.04 and −1.47 ± 0.01 for zalcitabine and BEA005, respectively. The degrees of plasma protein binding of zalcitabine (11% ± 4%) and BEA005 (18% ± 2%) were measured by microdialysis in vitro. The differences between zalcitabine and BEA005 with respect to the AUC ratio (P = 0.481), half-life in muscle (P = 0.279), and level of protein binding (P = 0.174) were not statistically significant. The differences were statistically significant in the case of the half-life in the brain (P = 0.032), clearance (P = 0.046), volume of distribution (P = 0.027) in muscle, and octanol/water partition coefficient (P = 0.019).

What Can We Learn from Sarcopenia with Curarisation in the Context of Cancer Surgery? A Review of the Literature

2019 ◽  
Vol 25 (28) ◽  
pp. 3005-3010
Author(s):  
Georges Samouri ◽  
Alexandre Stouffs ◽  
Lionel V. Essen ◽  
Olivier Simonet ◽  
Marc De Kock ◽  
...  
Keyword(s):  
Frail Elderly ◽  
Muscle Fibers ◽  
Motor Units ◽  
The Elderly ◽  
Hepatic Function ◽  
Volume Of Distribution ◽  
Neuromuscular Blocking ◽  
Cancer Surgery ◽  
Old People ◽  
Age Related

Introduction: The monitoring of the curarisation is a unique opportunity to investigate the function of the neuromuscular junction (NMJ) during cancer surgery, especially in frailty-induced and age-related sarcopenia. Method: We conducted a comprehensive literature review in PubMed, without any limit of time related to frailty, sarcopenia, age and response to neuromuscular blockers in the context of cancer surgery. Results: Several modifications appear with age: changes in cardiac output, a decrease in muscle mass and increase in body fat, the deterioration in renal and hepatic function, the plasma clearance and the volume of distribution in elderly are smaller. These changes can be exacerbated in cancer patients. We also find modifications of the NMJ: dysfunctional mitochondria, modifications in the innervation of muscle fibers and motor units, uncoupling of the excitation-contraction of muscle fibers, inflammation. : Neuromuscular blocking agents (NMBAs) compete with acetylcholine and prevent it from fixing itself on its receptor. Many publications reported guidelines for using NMBAs in the elderly, based on studies comparing old people with young people. : No one screened frailty before, and thus, no studies compared frail elderly and non-frail elderly undergoing cancer surgery. Conclusion: Despite many studies about curarisation in the specific populations, and many arguments for a potential interest for investigation, no studies investigated specifically the response to NMBAs in regard of the frailty-induced and age-related sarcopenia.

scholarly journals Extra Virgin Olive Oil Prevents the Age-Related Shifts of the Distribution of HDL Subclasses and Improves Their Functionality

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2235
Author(s):  
Alyann Otrante ◽  
Amal Trigui ◽  
Roua Walha ◽  
Hicham Berrougui ◽  
Tamas Fulop ◽  
...  
Keyword(s):  
Olive Oil ◽  
Virgin Olive Oil ◽  
Density Lipoprotein ◽  
Extra Virgin Olive Oil ◽  
The Elderly ◽  
High Density ◽  
Lipoprotein Cholesterol ◽  
Elderly Subjects ◽  
Age Related ◽  
Young Subjects

High-density lipoproteins (HDL) maintain cholesterol homeostasis through the role they play in regulating reverse cholesterol transport (RCT), a process by which excess cholesterol is transported back to the liver for elimination. However, RCT can be altered in the presence of cardiovascular risk factors, such as aging, which contributes to the increase in the incidence of cardiovascular diseases (CVD). The present study was aimed at investigating the effect of extra virgin olive oil (EVOO) intake on the cholesterol efflux capacity (CEC) of HDL, and to elucidate on the mechanisms by which EVOO intake improves the anti-atherogenic activity of HDL. A total of 84 healthy women and men were enrolled and were distributed, according to age, into two groups: 27 young (31.81 ± 6.79 years) and 57 elderly (70.72 ± 5.6 years) subjects. The subjects in both groups were given 25 mL/d of extra virgin olive oil (EVOO) for 12 weeks. CEC was measured using J774 macrophages radiolabeled with tritiated cholesterol ((3H) cholesterol). HDL subclass distributions were analyzed using the Quantimetrix Lipoprint® system. The HDL from the elderly subjects exhibited a lower level of CEC, at 11.12% (p < 0.0001), than the HDL from the young subjects. The CEC of the elderly subjects returned to normal levels following 12 weeks of EVOO intake. An analysis of the distribution of HDL subclasses showed that HDL from the elderly subjects were composed of lower levels of large HDL (L-HDL) (p < 0.03) and higher levels of small HDL (S-HDL) (p < 0.002) compared to HDL from the young subjects. A multiple linear regression analysis revealed a positive correlation between CEC and L-HDL levels (r = 0.35 and p < 0.001) as well as an inverse correlation between CEC and S-HDL levels (r = −0.27 and p < 0.01). This correlation remained significant even when several variables, including age, sex, and BMI as well as low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and glucose levels (β = 0.28, p < 0.002, and β = 0.24, p = 0.01) were accounted for. Consuming EVOO for 12 weeks modulated the age-related difference in the distribution of HDL subclasses by reducing the level of S-HDL and increasing the level of intermediate-HDL/large-HDL (I-HDL/L-HDL) in the elderly subjects. The age-related alteration of the CEC of HDL was due, in part, to an alteration in the distribution of HDL subclasses. A diet enriched in EVOO improved the functionality of HDL through an increase in I-HDL/L-HDL and a decrease in S-HDL.

Decreased Neutrophil Cyclic AMP Response to Isoprenaline Stimulation in the Elderly

1983 ◽  
Vol 65 (2) ◽  
pp. 155-157 ◽  
Author(s):  
T. G. Cotter ◽  
K. O'Malley
Keyword(s):  
Monoclonal Antibodies ◽  
Cyclic Amp ◽  
The Elderly ◽  
Population Heterogeneity ◽  
Elderly Subjects ◽  
Age Related ◽  
Significant Difference ◽  
Young Subjects ◽  
Drug Free

1. Neutrophils from drug-free elderly subjects produced approximately 50% less cyclic AMP in response to isoprenaline than did neutrophils from young subjects. A significant difference in basal cyclic AMP levels was also evident (elderly 2.8 ± 0.37; young 4.9 ± 0.36 pmol of cAMP/107 cells; P < 0.05). 2. With a range of anti-neutrophil monoclonal antibodies no evidence of age-related neutrophil population heterogeneity was found. 3. These findings indicate that the age-related decline in β-adrenoceptor responsiveness is not due to changes in the neutrophil population. 4. The present results support the hypothesis that there is a generalized decline in β-adrenoceptor-mediated responsiveness in the elderly.

scholarly journals Age features of arterial human kidney vessels

2019 ◽  
Vol 10 (4) ◽  
pp. 51-58
Author(s):  
O. A. Kaplunova
Keyword(s):  
Old Age ◽  
Human Kidney ◽  
The Elderly ◽  
Relative Content ◽  
Adaptive Capabilities ◽  
Age Related ◽  
Cortical Substance ◽  
Age Features ◽  
Aging People ◽  
Renal Vascular

Objective: to study the structural transformations of the architectonics of intra-organ renal arterial vessels in the age aspect.Materials and methods: 150 kidneys of people of diff erent age who died from the reasons which are not connected with diseases of cardiovascular and urinary systems are investigated. The studies were carried out using a set of methods: angiographic, macromicroscopic and morphometry.Results: with increasing age, a decrease in the number of vascular glomeruli in the kidney, the proportion of glomerular mass in the cortical substance of the kidney was found. In old age and in centenarians, a rare capillary network in the cortical substance of the kidney, tortuosity, narrowing and expansion of direct arterioles and capillaries in the cerebral substance was revealed. In old age and in centenarians, compared with adolescence, the relative content of arterial vessels in the cortical substance decreases by 6 times, in the juxtamedullary zone — by 4 and in the cortical substance — by 2 times.Conclusions: the large diameters of the juxtamedullary glomeruli and a large index of the relative content of arterial vessels in the juxtamedullary zone create prerequisites for possible juxtamedullary shunting with urgent adaptation in the norm. The decrease in these indicators in old age, the elderly and centenarians, obviously, explains the age-related decline in the adaptive capacity of the arterial bed of the kidneys. With increasing age, the range of adaptive capabilities of the renal vascular bed of aging people decreases compared to those of mature age. 

scholarly journals Compartmental Pharmacokinetics and Tissue Drug Distribution of the Pradimicin Derivative BMS 181184 in Rabbits

1998 ◽  
Vol 42 (10) ◽  
pp. 2700-2705 ◽  
Author(s):  
Andreas H. Groll ◽  
Tin Sein ◽  
Vidas Petraitis ◽  
Ruta Petraitiene ◽  
Diana Callender ◽  
...  
Keyword(s):  
Single Dose ◽  
Half Life ◽  
Peak Plasma ◽  
Volume Of Distribution ◽  
Multiple Dosing ◽  
Time Curve ◽  
Dose Administration ◽  
Single Dose Administration ◽  
Elimination Half ◽  
Dose Dependent

ABSTRACT The pharmacokinetics of the antifungal pradimicin derivative BMS 181184 in plasma of normal, catheterized rabbits were characterized after single and multiple daily intravenous administrations of dosages of 10, 25, 50, or 150 mg/kg of body weight, and drug levels in tissues were assessed after multiple dosing. Concentrations of BMS 181184 were determined by a validated high-performance liquid chromatography method, and plasma data were modeled into a two-compartment open model. Across the investigated dosage range, BMS 181184 demonstrated nonlinear, dose-dependent kinetics with enhanced clearance, reciprocal shortening of elimination half-life, and an apparently expanding volume of distribution with increasing dosage. After single-dose administration, the mean peak plasma BMS 181184 concentration (C max) ranged from 120 μg/ml at 10 mg/kg to 648 μg/ml at 150 mg/kg; the area under the concentration-time curve from 0 to 24 h (AUC0–24) ranged from 726 to 2,130 μg · h/ml, the volume of distribution ranged from 0.397 to 0.799 liter/kg, and the terminal half-life ranged from 4.99 to 2.31 h, respectively (P < 0.005 toP < 0.001). No drug accumulation in plasma occurred after multiple daily dosing at 10, 25, or 50 mg/kg over 15 days, although mean elimination half-lives were slightly longer. Multiple daily dosing at 150 mg/kg was associated with enhanced total clearance and a significant decrease in AUC0–24 below the values obtained at 50 mg/kg (P < 0.01) and after single-dose administration of the same dosage (P < 0.05). Assessment of tissue BMS 181184 concentrations after multiple dosing over 16 days revealed substantial uptake in the lungs, liver, and spleen and, most notably, dose-dependent accumulation of the drug within the kidneys. These findings are indicative of dose- and time-dependent elimination of BMS 181184 from plasma and renal accumulation of the compound after multiple dosing.

scholarly journals Preclinical Development of Inhalable D-Cycloserine and Ethionamide To Overcome Pharmacokinetic Interaction and Enhance Efficacy against Mycobacterium tuberculosis

2019 ◽  
Vol 63 (6) ◽  
Author(s):  
Rajeev Ranjan ◽  
Ashish Srivastava ◽  
Reena Bharti ◽  
Trisha Roy ◽  
Sonia Verma ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Bactericidal Activity ◽  
Half Life ◽  
Pharmacokinetic Interaction ◽  
Preclinical Development ◽  
Time Curve ◽  
Content Type ◽  
Concentration Time ◽  
Oral Doses ◽  
Plasma Half Life

ABSTRACT We compared the pharmacokinetics and efficacy of a combination of d-cycloserine (DCS) and ethionamide (ETO) via oral and inhalation routes in mice. The plasma half-life (t1/2) of oral ETO at a human-equivalent dose decreased from 4.63 ± 0.61 h to 1.64 ± 0.40 h when DCS was coadministered. The area under the concentration-time curve from 0 h to time t (AUC0–t) was reduced to one-third. Inhalation overcame the interaction. Inhalation, but not oral doses, reduced the lung CFU/g of Mycobacterium tuberculosis H37Rv from 6 to 3 log10 in 4 weeks, indicating bactericidal activity.

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