Site-Specific Pharmacokinetics and Pharmacodynamics of Intramuscular Meperidine in Elderly Postoperative Patients

1997 ◽  
Vol 31 (1) ◽  
pp. 23-28 ◽  
Author(s):  
Brian L Erstad ◽  
Mimi L Meeks ◽  
Hsiao-Hui Chow ◽  
William D Rappaport ◽  
Miriam L Levinson
Keyword(s):  
Breakthrough Pain ◽  
Tertiary Care ◽  
Volume Of Distribution ◽  
University Teaching ◽  
Pharmacokinetic Parameters ◽  
Maximum Plasma ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Pain Scores ◽  
Concentration Time ◽  
Pain Scales

OBJECTIVE: To examine and compare the pharmacokinetics and pharmacodynamics of meperidine when administered intramuscularly at gluteal and deltoid sites in elderly postoperative patients. DESIGN: Prospective, randomized investigation. SETTING: Tertiary care university teaching hospital. PATIENTS: Fourteen patients 60 years of age or older who were undergoing general surgery. INTERVENTION: A single dose of meperidine 0.75 mg/kg given intramuscularly at either a deltoid or gluteal site. MAIN OUTCOME MEASURES: Pharmacokinetic (based on concentration—time curves) and pharmacodynamic (i.e., pain scales, need for additional pain medication) comparisons were made, based on site of meperidine injection. RESULTS: No statistically significant differences were found in the maximum plasma concentration, volume of distribution, or clearance of meperidine by site of injection. Substantial interpatient variability in pharmacokinetic parameters was noted for both sites (range of maximum concentrations: 191–500 ng/mL gluteal, 166–374 ng/mL deltoid). Although pain scores were similar for the two groups, four of the patients in the group given gluteal injection required additional breakthrough pain management within 4 hours of meperidine injection compared with one patient in the group given deltoid injection. CONCLUSIONS: There is no obvious relationship between meperidine pharmacokinetic and pharmacodynamic parameters, regardless of intramuscular injection site. Breakthrough pain is common when patients are given intramuscular injections postoperatively, particularly when the gluteal route is used. When meperidine is used for analgesia in elderly postoperative patients, consideration should be given to more rapid and predictable routes (e.g., intravenous injection) of meperidine administration.

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 Telbivudine in Subjects with Various Degrees of Hepatic Impairment

2006 ◽  
Vol 50 (5) ◽  
pp. 1721-1726 ◽  
Author(s):  
Xiao-Jian Zhou ◽  
Thomas C. Marbury ◽  
Harry W. Alcorn ◽  
William B. Smith ◽  
Gloria Dubuc Patrick ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Plasma Concentration ◽  
Hepatitis B ◽  
Hepatic Impairment ◽  
Hepatic Function ◽  
Pharmacokinetic Parameters ◽  
Maximum Plasma ◽  
Concentration Time ◽  
Chronic Hepatitis B Virus ◽  
B Virus

ABSTRACT This study evaluated the effect of hepatic impairment on the pharmacokinetics of telbivudine, an investigational nucleoside antiviral for the treatment of chronic hepatitis B virus infection. Twenty-four subjects were assigned to four hepatic function groups (normal function and mild, moderate, and severe impairment, with six subjects in each group) on the basis of Child-Pugh scores. The subjects were administered a single oral dose of 600 mg telbivudine, and blood samples were collected over a 48-h interval for pharmacokinetic analyses. Telbivudine was well tolerated by all subjects. Telbivudine plasma concentration-time profiles were similar across the four hepatic function groups. The principal pharmacokinetic parameters of drug exposure, i.e., the maximum plasma concentration and area under the drug concentration-time curve, were comparable between subjects with various degrees of hepatic impairment and those with normal hepatic function. Results from this single-dose pharmacokinetic assessment therefore provide a pharmacologic rationale for further evaluation of the safety and efficacy of telbivudine in hepatitis B virus-infected patients with decompensated liver diseases.

scholarly journals Plasma pharmacokinetics of ciprofloxacin in sheep

1970 ◽  
Vol 6 (1) ◽  
pp. 93-97
Author(s):  
MS Islam ◽  
MMH Sikder ◽  
MA Awal ◽  
M Mostofa ◽  
AA Trisha
Keyword(s):  
Half Life ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Maximum Plasma ◽  
Sheep Model ◽  
First Order Kinetics ◽  
Healthy Sheep ◽  
Plasma Pharmacokinetics ◽  
Total Body

The study was carried out to determine the biodisposition kinetics of ciprofloxacin in sheep model in Department of Pharmacology, Bangladesh Agricultural University. Healthy sheep of both sexes (n=65) were divided into 13 groups, each consists of five and given a single dose of ciprofloxacin @ 5 mg/kg bwt intramuscularly .Blood sample was collected from each group of sheep at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10 and 12 hours interval respectively. Serum concentration of ciprofloxacin was determined by spectrophotometric method. The pharmacokinetic parameters were measured by single compartment open model and first order kinetics. The peak concentration of ciprofloxacin was 3.56±0.15mg/ ml, absorption half-life and biological half-life were 0.0846±1.79 and 1.75±0.15 h respectively. The apparent volume of distribution was found 35.54 mg/liter. The absorption rate constant was 8.188h-1, MRT was 2.647h-1 and total body clearances were found 16.88 h-1. These result suggested that a dose of 5 mg/kg bwt provides maximum plasma concentration and is effective in the control of many infectious diseases of sheep. Key words: Plasma pharmacokinetics, ciprofloxacin, sheep DOI = 10.3329/bjvm.v6i1.1344 Bangl. J. Vet. Med. (2008). 6 (1): 93-97

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.

scholarly journals P50 Individual variations in fentanyl pharmacokinetics and pharmacodynamics in preterm infants

2019 ◽  
Vol 104 (6) ◽  
pp. e37.3-e38
Author(s):  
J Kindblom ◽  
E Norman ◽  
A Rane ◽  
A-C Berg ◽  
U Schubert ◽  
...  
Keyword(s):  
Preterm Infants ◽  
Low Dose ◽  
Volume Of Distribution ◽  
High Dose ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Pain Scores ◽  
Individual Variations ◽  
Physiologic Parameters ◽  
New Formulation ◽  
Study Inclusion

BackgroundFentanyl pharmacokinetics and pharmacodynamics are lacking in preterm infants. Our aim was to study these and their relation with a new formulation of fentanyl 5 mg/mL for procedural pain.MethodsPreterm infants were given 0.5 (n=20, median gestational age 26.5; range 23.3–34.1 weeks) and 2 mg/kg (n=8, 27.4; 25.3–30.7 weeks) fentanyl, respectively, before skin-breaking procedures or tracheal intubation. Blood samples were collected after ten minutes, two, four, eight and 24 hours. Physiologic parameters were monitored and pain scores assessed.ResultsThe median fentanyl concentrations were 0.18, 0.15, 0.15 and 0.57, 0.37, 0.35ng/mL at 15–31 minutes, two and four hours and the half-lives were 1.6 to 20.5 or 4.1 to 32.6 hours for the low and high dose groups, respectively. A significant correlation was seen between weight at study inclusion and half-life (Spearman´s r = -0.9, p< 0.001), volume of distribution (r = -0.8, p < 0.01) and clearance (r = -0.9, p < 0.01) in the low dose group (n=9). Pain assessment results were not correlated to pharmacokinetic variables. Fentanyl was well tolerated.ConclusionThe inter-individual variation of fentanyl pharmacokinetics is large in preterm infants and the dose of 0.5 mg/kg seems too small for skin-breaking procedures.Disclosure(s)Nothing to disclose

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.

The Pharmacokinetics of Buserelin after Intramuscular Administration in Pigs and Cows

2021 ◽  
Author(s):  
Zhengrong Gao ◽  
Yu Liu ◽  
Yuxin Yang ◽  
Yuying Cao ◽  
Jicheng Qiu ◽  
...  
Keyword(s):  
Area Under The Curve ◽  
Apparent Volume ◽  
Ultra Performance Liquid Chromatography ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Maximum Plasma ◽  
Elimination Half ◽  
Liquid Chromatography Tandem Mass ◽  
Stability Method ◽  
Apparent Volume Of Distribution

Abstract Background: Buserelin is a LHRH agonist used for the treatment of hormone-dependent diseases in males and females. However, the pharmacokinetics of buserelin in pigs and cows are not clearly understood. This study was designed to develop a sensitive method to determine the concentration of buserelin and to investigate the pharmacokinetic parameters after intramuscular (i.m.) administration in pigs and cows. Results: A sensitive and rapid stability method based on ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was developed. The pharmacokinetic parameters of buserelin after i.m. administration were studies in five pigs and five cows at a single dose of 1 mg per pig and 3 mg per cow. The plasma kinetics were analyzed by WinNonlin 8.1.0 software using a non-compartmental model. The mean concentration area under the curve (AUC0-t) was 25.02 ± 6.93 h·ng/mL for pigs and 5.63 ±1.86 h·ng/mL for cows. The maximum plasma concentration (Cmax) and time to reach the maximum concentration (tmax) were 10.99 ± 2.04 ng/mL and 0.57 ± 0.18 h for pigs and 2.68 ± 0.36 ng/mL and 1.05 ±0.27 h for cows, respectively. The apparent volume of distribution (Vz) in pigs and cows was 80.49 ± 43.88 L and 839.88 ± 174.77 L, respectively. The elimination half-time (t1/2λz), and clearance (CL) were 1.29 ± 0.40 h and 41.15 ± 11.18 L/h for pigs and 1.13 ± 0.3 h and 545.04 ± 166.40 L/h for cows, respectively. No adverse effects were observed in any of the animals. Conclusion: This study extends previous studies describing the pharmacokinetics of buserelin following i.m. administration in pigs and cows. Further studies investigating other factors were needed to establish therapeutic protocol in pigs and cows and to extrapolate these parameters to others economic animals.

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.

Theophylline Disposition following Parenteral Feeding of Malnourished Patients

1993 ◽  
Vol 27 (7-8) ◽  
pp. 846-851
Author(s):  
Paul G. Cuddy ◽  
John F. Bealer ◽  
Elizabeth L. Lyman ◽  
L. Beatty Pemberton
Keyword(s):  
Parenteral Nutrition ◽  
Rate Constant ◽  
Tertiary Care ◽  
Elimination Rate ◽  
Volume Of Distribution ◽  
Elimination Rate Constant ◽  
Parenteral Feeding ◽  
Maximum Plasma ◽  
Serum Theophylline ◽  
Theophylline Disposition

OBJECTIVE: To investigate the effect of parenteral nutrition on theophylline disposition in malnourished patients. DESIGN: Before-after trial. SETTING: Tertiary care center. PATIENTS: Ten patients with historic, anthropometric, and laboratory evidence of malnutrition. INTERVENTIONS: Patients received two 5-mg/kg intravenous infusions of theophylline separated by at least 48 hours of glucose-based parenteral nutrition providing the entire estimated nutritional requirements. MAIN OUTCOME MEASURES: Following each theophylline administration, serum theophylline samples were collected over a 24-hour period for delineation of maximum plasma concentrations, volume of distribution, elimination rate constant, clearance, and area under the curve. RESULTS: Peak plasma theophylline concentrations were significantly lower prior to feeding (5.3 μmol/L, 95 percent confidence interval [CI] 0.78–10.0 μmol/L, p=0.028). Volume of distribution decreased after parenteral feeding (0.08 L/kg, 95 percent CI 0.006–0.15 L/kg, p=0.037). The elimination rate of theophylline increased after parenteral feeding reflected by an increase in the elimination rate constant (0.06 h1, 95 percent CI 0.01–0.10 h−1, p=0.023). CONCLUSIONS: This study suggests that parenteral nutrition using a glucose-based solution acutely influences theophylline disposition in malnourished patients.

scholarly journals Pharmacokinetics of toltrazuril and its metabolites toltrazuril sulphoxide and toltrazuril sulphone in pregnant and non-pregnant goats

2021 ◽  
Vol 90 (4) ◽  
pp. 383-390
Author(s):  
Sara T. Elazab ◽  
Nahla S. Elshater ◽  
Ahmed E. Elweza
Keyword(s):  
Plasma Concentration ◽  
Volume Of Distribution ◽  
Maximum Plasma ◽  
Time Curve ◽  
Concentration Time ◽  
Elimination Half ◽  
Plasma Concentration Time Curve ◽  
Group 2 ◽  
Post Therapy ◽  
Group 1

The pharmacokinetic characteristics of toltrazuril (TZR) and its metabolites toltrazuril sulphoxide (TZR.SO) and toltrazuril sulphone (TZR.SO2) were assessed in non-pregnant and pregnant goats. Ten healthy Baladi female goats were allocated into two groups (n = 5 per group): non-pregnant goats (group 1) and pregnant goats at 2–3 months of gestation (group 2). Toltrazuril was administered once orally to all goats at 20 mg/kg. Plasma samples were collected at 0 (before TZR administration), 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72 h and 5, 7, 9, 12, 16, 20, 24, 27, 30, and 35 days post therapy to measure the concentrations of TZR and its metabolites. In pregnant goats, the maximum plasma concentration (Cmax), time to reach Cmax (Tmax), and the area under the plasma concentration-time curve from time zero to the last sample (AUC0-last) of TZR were significantly higher (P < 0.05) compared to the non-pregnant ones, whereas the volume of distribution (Vz_F_obs) and clearance (Cl_F_obs) were significantly lower (P < 0.05) in pregnant goats. No significant differences were observed in the elimination half-life (T1/2λz), and mean residence time (MRT) between the two groups. In non-pregnant goats, TZR.SO and TZR.SO2 could be detected in plasma until 12 and 30 days, respectively; whereas in pregnant goats, they were quantified up to 16 and 35 days, respectively. Conclusively, TZR was well absorbed and rapidly metabolized to TZR.SO and TZR.SO2, after oral dosing in goats. Pregnancy caused significant alterations in some of the pharmacokinetic indicators of TZR and its metabolites in goats.

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