Gentamicin Pharmacokinetics in Elderly Patients with Normal Renal Function

1994 ◽  
Vol 10 (1) ◽  
pp. 14-17 ◽  
Author(s):  
Ji M. Koo ◽  
Donald R. Miller ◽  
Charles D. Peterson
Keyword(s):  
Renal Function ◽  
Elderly Patients ◽  
Normal Renal Function ◽  
Medical Center ◽  
Elimination Rate ◽  
The Elderly ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Trough Concentrations ◽  
The Mean

Objective: To establish the pharmacokinetic parameters of gentamicin in elderly patients and to compare predicted concentrations based on the Dettli method, with actual concentrations. Design: Measurement of gentamicin concentrations and pharmacokinetic parameters in a consecutive patient sample with comparison to ones predicted by the Dettli method. Setting: Medical and surgical units in a Veterans Affairs Medical Center. Patients: Forty-six consecutive elderly men treated with gentamicin for documented or presumed infection and had stable, normal renal function. Main Outcome Measures: The following information was calculated or measured: elimination rate constant (kel), elimination half-life, volume of distribution (Vd), and peak and trough concentrations. Results: The mean kel (0.16 ± 0.05 h−1) was not significantly different (p=0.2) from the Dettli method prediction, and the mean Vd (0.36 ± 0.1 L/kg) was 37 percent higher than that usually reported. Actual peak and trough concentrations were significantly lower (both p<0.01) than predicted concentrations. Conclusions: Based on our findings, higher than recommended loading doses and longer dosage intervals may be required in the elderly. The Dettli method is useful to estimate kel in the elderly.

Reevaluation of Gentamicin Dosing in the Neonatal Population

1995 ◽  
Vol 11 (3) ◽  
pp. 105-109
Author(s):  
Thomas M Gray
Keyword(s):  
Rate Constant ◽  
Gestational Age ◽  
Trough Concentration ◽  
Elimination Rate ◽  
Retrospective Chart Review ◽  
Volume Of Distribution ◽  
Full Term ◽  
Pharmacokinetic Parameters ◽  
Trough Concentrations ◽  
Neonatal Population

Objective: To determine whether current recommendations for gentamicin dosing in full-term newborns yield a serum peak concentration of 6–7 μg/mL and a trough concentration less than 2 μg/mL in treating suspected neonatal sepsis. Design: Two-year retrospective chart review. Setting: Community hospital. Results: Sample consisted of 175 newborns with a gestational age ranging from 36 to 43 weeks and 188 sets of concentrations. Pharmacokinetic parameters were calculated using a one-compartment, first-order elimination model and were reported as follows: volume of distribution 0.59 kg/L, elimination rate constant (ke) 0.11 h−1 (half-life [t1/2] 6.8 h) at 36–37 weeks of age, with a significant change (p < 0.05) in rate constant occurring at 38–43 weeks of life, and ke 0.12 h−1 (t1/2 6.0 h) when using a two-tailed, two-sample t-test. Extrapolated mean peak concentrations were 5.8 ± 1.2 μg/mL and trough concentrations were 1.5 ± 0.5 μg/mL. Furthermore, 14% of newborns had an extrapolated trough concentration of 2.0 μg/mL or more. Conclusions: The current 2.5-mg/kg dosage is appropriate for the neonatal population studied. However, to decrease the number of potentially toxic trough concentrations, the initial dosing interval should be extended to every 18 hours for full-term neonates (>37 weeks gestation) with normal kidney function and for neonates with a gestational age of 36–37 weeks.

scholarly journals Evaluation of pharmacokinetics of warfarin from validated pharmacokinetic-pharmacodynamic model

ADMET & DMPK ◽  
2021 ◽  
Author(s):  
Kannan Sridharan ◽  
Rashed Al Banna ◽  
Aysha Husain
Keyword(s):  
Elimination Rate ◽  
Liver Weight ◽  
International Normalized Ratio ◽  
Volume Of Distribution ◽  
Pharmacodynamic Model ◽  
Pharmacokinetic Parameters ◽  
Maximum Plasma ◽  
The Mean ◽  
Study Participants ◽  
The Relationship

Background: Pharmacokinetics of warfarin has not been described in our population. We derived the pharmacokinetic parameters from a validated pharmacokinetic-pharmacodynamic model. Methods: Patients receiving warfarin for at least 6 months were recruited and their demographic characteristics, prothrombin time international normalized ratio (PT-INR), warfarin doses and concomitant drugs were collected. Using a validated pharmacokinetic-pharmacodynamic model, we predicted maximum plasma concentration (Cmax), total clearance (CL), volume of distribution (Vd) and elimination rate (k). Warfarin sensitive index (WSI) and warfarin composite measures (WCM) were estimated from the dose and INR values. Liver weight was predicted using validated formula. Results: Two-hundred and twenty patients were recruited. The following were the predicted pharmacokinetic parameters: Cmax (mg/L) was 5.8 (0.4); k (L/day) was 1 (0.1); CL (L/day) was 2.1 (0.2); and Vd (L) was 7.6 (0.2). Patients with Cmax and elimination rate outside the mean+1.96 SD had significantly lower WSI and higher WCM. Significant correlations were observed between Cmax with CL, Vd, and k of warfarin. Significant correlations were also observed between CL and Vd of warfarin with liver weight of the study participants. Conclusion: We predicted pharmacokinetic parameters of warfarin from the validated pharmacokinetic-pharmacodynamic model in our population. More studies are needed exploring the relationship between various pharmacodynamic indices of warfarin and pharmacokinetic parameters of warfarin.

Phenobarbital Pharmacokinetics in Infants Using Saliva as a Biologic Fluid

1994 ◽  
Vol 10 (6) ◽  
pp. 250-254
Author(s):  
Stella Gutierrez ◽  
Marta Vázquez ◽  
Amanda Amodio ◽  
Gustavo Giachetto ◽  
Diana Moller ◽  
...  
Keyword(s):  
Medical Center ◽  
Randomized Study ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Loading Dose ◽  
Seizure Disorders ◽  
Elimination Half ◽  
Significant Difference ◽  
Daily Dose ◽  
Trough Concentrations

Objective: To determine the pharmacokinetic parameters of phenobarbital in infants, using saliva as a biologic fluid, and to correlate the parameters obtained from saliva data with those obtained from plasma data. Design: A prospective, randomized study. Setting: Hospitalized patients at the Medical Center Pereira Rossell, a pediatric hospital in Montevideo, Uruguay. Patients: Sixteen infants with seizure disorders were included in the study. None of them was treated with other medications. Interventions: A direct intravenous loading dose of phenobarbital 10 mg/kg was administered, followed by a maintenance dosage of 5 mg/kg/d (once- or twice-daily dosing) given 12 hours after the loading dose. Main Outcome Measures: Saliva and plasma samples were obtained 6 and 12 hours after the loading dose and 3 days after the initiation of the maintenance dose (trough sample): the samples were analyzed by HPLC and the elimination half-life (t1/2), the volume of distribution (Vd), and the percentage of unbound drug in plasma (UDP) were calculated. Results: The t1/2 obtained from plasma and saliva data was 30 hours; the Vd was 0.73 L/kg from plasma data and 2.4 L/kg from saliva data; and the UDP was 75 percent. Trough concentrations showed no significant difference between treatments. Conclusions: Saliva is a useful biologic fluid to determine phenobarbital pharmacokinetic parameters, mainly in pediatric patients. Moreover, a single daily dose of phenobarbital is sufficient to obtain therapeutic concentrations.

Evaluation of an Empirical Dosing Schedule for Gentamicin in Neonates

1988 ◽  
Vol 22 (7-8) ◽  
pp. 618-622 ◽  
Author(s):  
Mary R. Bloome ◽  
Amy J. Warren ◽  
Linda Ringer ◽  
Paul C. Walker
Keyword(s):  
Age Groups ◽  
Elimination Rate ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Dosing Schedule ◽  
Significant Relationships ◽  
Trough Serum ◽  
Postconceptional Age ◽  
Trough Concentrations ◽  
Gentamicin Therapy

The standard gentamicin dosing recommendations for neonates appear to be inappropriate because they fail to consider the influence of neonatal development on gentamicin pharmacokinetics. Recent reports have emphasized that the standard regimens of 2.5 mg/kg q8–12h produce steady-state trough serum concentrations > 2 μg/ml in up to 91 percent of preterm infants of less than 35 weeks' gestation. A new dosing schedule based on postconceptional age (PCA) was developed to provide a better guideline for initiating and maintaining gentamicin therapy in neonates: PCA greater than 34 weeks, 2.5 mg/kg iv q12h; PCA 28–34 weeks, 2.5 mg/kg iv q16h; PCA less than 28 weeks, 2.5 mg/kg iv q24h. The new dosing schedule reduced the number of neonates with elevated trough concentrations (>2 μg/ml) from 68.4 percent to 33–40 percent. Pharmacokinetic parameters for gentamicin in the various PCA groups were determined. Volume of distribution was constant across age groups (0.5 ± 0.09 L/kg). Elimination rate constants (kel), half-lives, and clearance rates (Cl) ranged from 0.069 ± 0.02 to 0.14 ± 0.04h−1, 10.71 ± 2.92 to 6.04 ± 1.24 h, and 0.58 ± 0.25 to 0.93 ± 0.24 ml/kg/min, respectively. Significant relationships were found between kel and Cl and patient age and weight; significant correlations were found between actual and estimated (based on PCA and weight) kel and Cl. Variability in kel and Cl estimated was considerable in spite of the correlations. The observed variability stresses again the need for pharmacokinetic monitoring of gentamicin therapy in neonates.

scholarly journals Studies on effects of lactose on experimental Trypanosoma vivax infection in Zebu cattle. 1. Plasma kinetics of intravenously administered lactose at onset of infection and pathology

2008 ◽  
Vol 75 (2) ◽  
Author(s):  
M. Y. Fatihu ◽  
S. Adamu ◽  
I. A. Umar ◽  
N. D.G. Ibrahim ◽  
L. O. Eduvie ◽  
...  
Keyword(s):  
Muscular Atrophy ◽  
Elimination Rate ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Zebu Cattle ◽  
Trypanosoma Vivax ◽  
Histopathological Lesions ◽  
The Mean ◽  
Total Body

Lactose in normal saline was administered intravenously to a group of Zebu cattle infected with Trypanosoma vivax to determine the bloodplasma kinetics at onset of an experimental infection and its ability to protect tissues against damage as part of preliminary studies to determine its suitability for use in the treatment of trypanosomosis. Significant (P <0.01) higher lactose concentrations were observed in the T. vivax-intecled bulls at 30 min and 1h (P< 0.05) post-infectio (p.i.) and by 4 h p.i. the plasma lactose remained above the level prior to infusion, after which it fell slightly below the preinfusion level in the uninfected group. Calculated pharmacokinetic parameters revealed delayed excretion of lactose in the T. vivax-intected group soon after infection. The total body clearance (C/B )was significantly (P < 0.05) reduced. The biological half-life (t1/2), elimination rate constant (kel) and apparent volume of distribution (Vd) were relatively decreased (P > 0.05) as a result of the T. vivax infection. Retention of lactose in the plasma was attributed to decreased plasma clearance l.t is suggested that the presence of trypanosomes in circulation rather than organic lesions could have been responsible for the delay observed in the excretion of lactose.At 12 weeks p.i., when the experiment was terminated, the group infected and given lactose infusion (despiteh igherp arasitaemia) had no gross or histopathological lesions in the brain, spleen, lymphnodes, heart, kidneys, liver and testes. However, the group infected but not infused with lactose were emaciated, had pale mucosae, watery blood, general muscular atrophy, serous atrophy of coronary fat and other adiposet issue, hepatomegalys, plenomegalys, wollen and oedematous lymph nodes, all of which are suggestive of trypanosomosis. Histopathological lesions included arrowing of Bowman's space and hypercellularity of glomerular tufts in the kidneys with the mean glomerula truft nucleairn dices (GTNs) in the group significantly higher (P <0.01)than the mean GTNs of the lactoseinfused and control bulls. Degenerative changes occurred in the myocardium, spleen, testes and epididymides. The tesicular and epididymal lesions are indicative of male reproductive dysfunction.

scholarly journals Effect of polyaspartic acid on pharmacokinetics of gentamicin after single intravenous dose in the dog.

1996 ◽  
Vol 40 (5) ◽  
pp. 1237-1241 ◽  
Author(s):  
T Whittem ◽  
K Parton ◽  
K Turner
Keyword(s):  
Aspartic Acid ◽  
Elimination Rate ◽  
Volume Of Distribution ◽  
Intravenous Dose ◽  
Pharmacokinetic Parameters ◽  
Therapeutic Drug ◽  
Peripheral Compartment ◽  
Single Intravenous Dose ◽  
Polyaspartic Acid ◽  
Peripheral Tissues

The effects of poly-L-aspartic acid on the pharmacokinetics of gentamicin were examined by using a randomized crossover trial design with the dog. When analyzed according to a three-compartment open model, poly-L-aspartic acid reduced some first-order rate equation constants (A3, lambda 1, and lambda 3), the deep peripheral compartment exit microconstant (k31), the elimination rate constant (k(el)), and the area under the concentration-time curve from 0 to 480 h (AUC0-480) (0.21-, 0.60-, 0.26-, 0.27-, 0.72-, and 0.76-fold, respectively; P < 0.05) but increased the volume of distribution at steady state (Vss), the volume of distribution calculated by the area method (V(area)), the apparent volume of the peripheral compartment (Vp), and all mean time parameters. These results suggested that poly-L-aspartic acid increased the distribution of gentamicin to or binding within the deep peripheral compartment and that poly-L-aspartic acid may have delayed gentamicin transit through the peripheral tissues. In contrast, poly-L-aspartic acid did not alter pharmacokinetic parameters relevant to the central or shallow peripheral compartments to a clinically significant extent. Although gentamicin's pharmacokinetic parameters of relevance to therapeutic drug monitoring were not directly altered, this study has provided pharmacokinetic evidence that poly-L-aspartic acid alters the peripheral distribution of gentamicin. This pharmacokinetic interaction occurred after a single intravenous dose of each drug. Therefore, this interaction should be investigated further, before polyaspartic acid can be considered for use as a clinical nephroprotectant.

MO403ACUTE KIDNEY INJURY IN ELDERLY: EPIDEMIOLOGICAL, CLINICAL AND ETIOLOGICAL FEATURES

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Mouna Malki abidi ◽  
Rajaa Aoudia ◽  
Soumaya Chargui ◽  
Imen Gorsane ◽  
Mouna Jerbi ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Injury ◽  
The Elderly ◽  
Major Interest ◽  
The Mean ◽  
Renal Aging ◽  
End Stage ◽  
Iatrogenic Origin

Abstract Background and Aims Acute kidney injury (AKI) is common in the elderly due to physiologic renal aging and underlying pathologies. Few studies focused on AKI in Tunisian elderly. The aim of our study was to highlight the epidemiological, clinical, etiological, therapeutic, and progressive characteristics of AKI in elderly. Method We conducted a descriptive retrospective study of AKI in patients admitted to our department over a period of 04 years from 01/01/2014 to 31/12/2017. Results We collected 40 patients including 25 women and 15 men with a sex ratio of 1.66. The mean age was 74 [65-87] years. We noted the presence of pre-existing chronic kidney disease in 58% of cases, diabetes in 50% of cases and hypertension in 73% of cases. Polypharmacy was found in 40% of cases. AKI was symptomatic in 80% of cases and found on a routine check-up in 20% of cases. Mean creatinine was 612+/-334 µmol/l. AKI was pre-renal in 37% and parenchymal in 63% of cases. Iatrogenic origin was found in 33% of cases. Renal biopsy was performed for diagnostic purposes in 6 cases. Haemodialysis was necessary in 50% of cases. Etiopathogenic treatment was initiated in 73% of cases. Intra-hospital mortality was 10%, recovery of renal function (RF) was partial in 40 % of cases and total in 20 % of cases. Follow-up time was 16 +/- 23.2 months. And at the last news, recovery of renal function (RF) was partial in 7 cases and total in 10 cases, 6 patients kept a chronic renal failure (CRF), among them 3 cases had and end-stage of CRF. Conclusion AKI is a frequent pathology in the elderly and its severity is linked to mortality and the transition to chronicity. Iatrogenic causes are frequent and preventable in this population, hence the major interest of prevention.

scholarly journals Pharmacokinetics of lamivudine in human immunodeficiency virus-infected patients with renal dysfunction.

1996 ◽  
Vol 40 (6) ◽  
pp. 1514-1519 ◽  
Author(s):  
A E Heald ◽  
P H Hsyu ◽  
G J Yuen ◽  
P Robinson ◽  
P Mydlow ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Renal Function ◽  
Renal Impairment ◽  
Normal Renal Function ◽  
Severe Renal Impairment ◽  
Moderate Renal Impairment ◽  
Pharmacokinetic Parameters ◽  
Geometric Means ◽  
Immunodeficiency Virus

The purpose of this study was to determine the safety and pharmacokinetics of lamivudine (3TC), a nucleoside analog that has shown potent in vitro and recent in vivo activity against human immunodeficiency virus. Sixteen human immunodeficiency virus-infected patients, six with normal renal function (creatinine clearance [CLCR], > or = 60 ml/min), four with moderate renal impairment (CLCR, 10 to 40 ml/min), and six with severe renal impairment (CLCR, < 10 ml/min), were enrolled in the study. After an overnight fast, patients were administered 300 mg of 3TC orally. Blood was obtained before 3TC administration and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 32, 40, and 48 h afterward. Timed urine collections were performed for patients able to produce urine. Serum and urine were assayed for 3TC by reverse-phase high-performance liquid chromatography with UV detection. Pharmacokinetic parameters were calculated by using standard noncompartmental techniques. The peak concentration of 3TC increased with decreasing renal function; geometric means were 2,524, 3,538, and 5,684 ng/ml for patients with normal renal function, moderate renal impairment, and severe renal impairment, respectively. The terminal half-life also increased with decreasing renal function; geometric means were 11.5, 14.1, and 20.7 h for patients with normal renal function, moderate renal impairment, and severe renal impairment, respectively. Both oral and renal clearances were linearly correlated with CLCR. A 300-mg dose of 3TC was well tolerated by all three patient groups. The pharmacokinetics of 3TC is profoundly affected by impaired renal function. Dosage adjustment, by either dose reduction or lengthening of the dosing interval, is warranted.

scholarly journals Pharmacokinetics of Intravenous Piperacillin Administration in Patients Undergoing On-Line Hemodiafiltration

2009 ◽  
Vol 53 (8) ◽  
pp. 3266-3268 ◽  
Author(s):  
Kook-Hwan Oh ◽  
Chiweon Kim ◽  
Hankyu Lee ◽  
Hajeong Lee ◽  
Ji Yong Jung ◽  
...  
Keyword(s):  
Standard Deviation ◽  
Total Body Clearance ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Recovery Method ◽  
Elimination Half ◽  
On Line ◽  
The Mean ◽  
Total Body ◽  
Body Clearance

ABSTRACT The pharmacokinetic characteristics of piperacillin sodium were studied in five volunteers undergoing on-line hemodiafiltration (HDF). The subjects were given 2 g of piperacillin sodium intravenously over 1 min and placed on on-line HDF for 4 h starting at 60 min after the piperacillin infusion. Noncompartmental models were employed for estimation of the pharmacokinetic parameters, and intradialytic piperacillin clearance was calculated by the recovery method. The mean volume of distribution and the elimination half-life were 0.27 ± 0.13 liter/kg (mean ± standard deviation) and 1.1 ± 0.6 h, respectively. The total body clearance of piperacillin was 0.19 ± 0.08 liter/h/kg. Piperacillin clearance through on-line HDF was 0.11 ± 0.06 liter/h/kg. The mean serum piperacillin concentration was 4.0 ± 1.9 μg/ml at the end of the 4-h on-line HDF session. The concentration of infused piperacillin recovered in the dialysate was 527 ± 236 mg (26.3% ± 11.8%). We suggest the replacement of 500 mg of piperacillin after each on-line HDF session.

scholarly journals Population Pharmacokinetic Analysis of Vancomycin Using Serum Cystatin C as a Marker of Renal Function

2009 ◽  
Vol 54 (2) ◽  
pp. 778-782 ◽  
Author(s):  
Akihiro Tanaka ◽  
Tetsuya Aiba ◽  
Takashi Otsuka ◽  
Katsuya Suemaru ◽  
Tatsuya Nishimiya ◽  
...  
Keyword(s):  
Renal Function ◽  
Cystatin C ◽  
Predictive Performance ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Population Pharmacokinetic ◽  
Serum Cystatin C ◽  
Serum Cystatin ◽  
New Model ◽  
The Mean

ABSTRACT We determined the population pharmacokinetics of vancomycin (VAN) using the glomerular filtration rate (GFR) estimated from the serum cystatin C concentration. We examined the predictive performance of the trough serum VAN concentration for determination of the initial dose by using a new model for the analysis of the population pharmacokinetic parameters. Data for 86 patients were used to estimate the values of the population pharmacokinetic parameters. Analysis with a nonlinear mixed-effects modeling program was done by using a one-compartment model. Data for 78 patients were used to evaluate the predictive performance of the new model for the analysis of population pharmacokinetic parameters. The estimated GFR values determined by using Hoek's formula correlated linearly with VAN clearance (VAN clearance [ml/min] = 0.825 × GFR). The mean volume of distribution was 0.864 (liters/kg). The interindividual variability of VAN clearance was 19.8%. The accuracy of the prediction determined by use of the new model was statistically better than that determined by use of the Japanese nomogram-based model because the 95% confidence interval (−3.45 to −1.38) of the difference in each value of the mean absolute error (−2.41) did not include 0. Use of the serum cystatin C concentration as a marker of renal function for prediction of serum VAN concentrations may be useful.

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