scholarly journals Pharmacokinetics of Boldine in Control and Mrp2-Deficient Rats

2016 ◽  
pp. S489-S497 ◽  
Author(s):  
J. CERMANOVA ◽  
A. PRASNICKA ◽  
E. DOLEZELOVA ◽  
L. ROZKYDALOVA ◽  
M. HROCH ◽  
...  
Keyword(s):  
Renal Clearance ◽  
Intravenous Administration ◽  
Half Life ◽  
Bolus Dose ◽  
Volume Of Distribution ◽  
Total Clearance ◽  
Lewis Rats ◽  
Biliary Clearance ◽  
Dose Study ◽  
Clearance Study

The aim of the present study was to describe the currently poorly understood pharmacokinetics (PK) of boldine in control rats (LW, Lewis rats), and Mrp2 transporter-deficient rats (TR-). Animals from the LW and TR- groups underwent a bolus dose study with 10 mg/kg of boldine applied either orally or intravenously in order to evaluate the major PK parameters. The TR- rats demonstrated significantly reduced total clearance with prolonged biological half-life (LW 12±4.6 versus TR- 20±4.4 min), decreased volume of distribution (LW 3.2±0.4 l/kg versus TR- 2.4±0.4 l/kg) and reduced bioavailability (LW 7 % versus TR- 4.5 %). Another set of LW and TR- rats were used for a clearance study with continuous intravenous administration of boldine. The LW rats showed that biliary and renal clearance formed less than 2 % of the total clearance of boldine. The treatment of samples with β glucuronidase showed at least a 38 % contribution of conjugation reactions to the overall clearance of boldine. The TR- rats demonstrated reduced biliary clearance of boldine and its conjugates, which was partly compensated by their increased renal clearance. In conclusion, this study presents the PK parameters of boldine and shows the importance of the Mrp2 transporter and conjugation reactions in the elimination of the compound.

scholarly journals Pharmacokinetics of CS-023 (RO4908463), a Novel Parenteral Carbapenem, in Healthy Male Caucasian Volunteers

2006 ◽  
Vol 50 (12) ◽  
pp. 4186-4188 ◽  
Author(s):  
Takahiro Shibayama ◽  
Yoko Matsushita ◽  
Takashi Hirota ◽  
Toshihiko Ikeda ◽  
Shogo Kuwahara
Keyword(s):  
Urinary Excretion ◽  
Healthy Volunteers ◽  
Renal Clearance ◽  
Half Life ◽  
Volume Of Distribution ◽  
Total Clearance ◽  
Healthy Male ◽  
Cumulative Urinary Excretion

ABSTRACT The CS-023 concentration in plasma after administration by infusion to healthy volunteers at a dose of 700 mg was decreased, with a half-life of 1.7 h, and the cumulative urinary excretion was 59.4% of the dose. The total clearance, renal clearance, and volume of distribution were 8.12 liters/h, 4.14 liters/h, and 17.2 liters, respectively.

scholarly journals Methadone Pharmacokinetics in Geriatric Critically Ill Patients Following Intramuscular and Intravenous Administration: A Pilot Stud

2020 ◽  
Author(s):  
Safoura Beik Rassouli ◽  
Mohammad Reza Rouini ◽  
Farhad Najmeddin ◽  
Azin Gheimati ◽  
Ali A Golabchifar ◽  
...  
Keyword(s):  
Pain Management ◽  
Critically Ill ◽  
Intravenous Administration ◽  
Critically Ill Patients ◽  
Half Life ◽  
Serum Levels ◽  
Volume Of Distribution ◽  
Icu Patients ◽  
Potential Alternative ◽  
Pharmacokinetic Behavior

Background: Methadone is used for the pain management worldwide. Its special characteristics make it a potential alternative for pain management in critically ill and geriatric patients. Due to lack of studies in this population, we aimed to compare the pharmacokinetic behavior of Methadone following intramuscular and intravenous administration in geriatric ICU patients and with previously reports in healthy volunteers. Methods: According to the limitations in ICU setting, we could include 11 patients over 65 years old, who required opioid for pain relief in this study. Patients were randomized to receive 5 mg of Methadone IM or IV injection every 8 hours for 6 days. The Methadone plasma level detected with LC-mass tandem mass spectrometry, and pharmacokinetics parameters were evaluated for each subject in both 1st and 6th days of treatment. Results: Based on our results, bioavailability of intramuscular Methadone in geriatric ICU patients was low and less than 40% of the dose was absorbed within first 12 hours. The volume of distribution of Methadone in the first day was significantly lower than the previously reported values in healthy subjects and significantly increased during these 6 days. The Methadone half-life in this population also significantly increased through this period. Conclusion: Pharmacokinetic behavior of Methadone in geriatric ICU patients is unpredictable. Reduced volume of distribution and half-life may be observed initially, following with an increase to the normal range. It seems that IM administration of Methadone in geriatric critically ill patients may not provide target analgesic Methadone serum levels.

scholarly journals Pharmacokinetics of gentamicin at traditional versus high doses: implications for once-daily aminoglycoside dosing.

1997 ◽  
Vol 41 (5) ◽  
pp. 1115-1119 ◽  
Author(s):  
D J Demczar ◽  
A N Nafziger ◽  
J S Bertino
Keyword(s):  
Half Life ◽  
Pharmacokinetic Model ◽  
Infusion Pump ◽  
Volume Of Distribution ◽  
High Dose ◽  
Time Data ◽  
Single Dose Study ◽  
Once Daily ◽  
Dose Study ◽  
High Doses

Two doses of gentamicin (2 and 7 mg/kg of body weight) were administered to 11 healthy volunteers in a randomized, crossover single-dose study to compare their pharmacokinetics. Doses were infused over 1 h with a syringe infusion pump, and 14 concentrations in sera were obtained over an 8-h period. Concentration in serum versus time data were fitted to a two-compartment pharmacokinetic model. In addition, to mimic the clinical setting, subjects' data were fitted by the Sawchuk-Zaske method. Distributional and postdistributional peak concentrations, along with the last obtained concentration in serum, were utilized to compare the following pharmacokinetic variables: volume of distribution at steady state (Vss), half-life, clearance (CL), and maximum concentration in serum (Cmax). With two-compartment pharmacokinetic fitting, significant differences in distribution half-life (average, 21.8 and 41.6 min [P < or = 0.05]) and gentamicin CL (76.6 +/- 6.6 and 67.2 +/- 4.2 ml/min/1.73 m2 [P < or = 0.001]) were found between traditional-dose and high-dose groups, respectively. When the data for concentrations in sera were fitted to a one-compartment pharmacokinetic model by using either the distributional or the postdistributional Cmax, statistically significant differences (P < or = 0.001) were found between Vss, half-life, CL, and Cmax values for both dosage groups. The results show that the pharmacokinetics of gentamicin at a large dose differ significantly from those at the traditional dose. This information has direct implications for once-daily aminoglycoside (ODA) literature when the Cmax values reported are distributional and therefore show falsely high Cmax/MIC ratio estimates. In addition, ODA nomogram dosing tools developed with distributional Cmax values are probably inaccurate.

Comparative metabolic clearance rate, volume of distribution and plasma half-life of human β-lipotropin and acth

Life Sciences ◽  
1978 ◽  
Vol 23 (23) ◽  
pp. 2323-2330 ◽  
Author(s):  
Anthony S. Liotta ◽  
Choh Hao Li ◽  
George C. Schussler ◽  
Dorothy T. Krieger
Keyword(s):  
Clearance Rate ◽  
Half Life ◽  
Volume Of Distribution ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Plasma Half Life

3. Half-Life and Volume of Distribution

1968 ◽  
Vol 2 (5) ◽  
pp. 126-133 ◽  
Author(s):  
John G. Wagner
Keyword(s):  
Half Life ◽  
Volume Of Distribution

scholarly journals Pharmacokinetics of Once Daily Intraperitoneal Cefazolin in Continuous Ambulatory Peritoneal Dialysis Patients

2000 ◽  
Vol 11 (6) ◽  
pp. 1117-1121
Author(s):  
CHAI LUAN LOW ◽  
KAMANI GOPALAKRISHNA ◽  
WAI CHOONG LYE
Keyword(s):  
Peritoneal Dialysis ◽  
Continuous Ambulatory Peritoneal Dialysis ◽  
Half Life ◽  
Volume Of Distribution ◽  
Hplc Method ◽  
Dialysis Patients ◽  
Suitable Alternative ◽  
Once Daily ◽  
Cefazolin Sodium ◽  
Plasma Half Life

Abstract. This study determined the pharmacokinetic characteristics of once daily intraperitoneal (IP) cefazolin in continuous ambulatory peritoneal dialysis (CAPD) patients. Each of the 10 volunteer CAPD patients without active peritonitis received a single IP dose of 1 g of cefazolin sodium for a 6-h dwell. All patients underwent a fixed CAPD regimen comprising a first 6-h dwell followed by two 3-h dwells and a final 12-h overnight dwell. Blood and dialysate samples were collected at 0, 0.5, 1, 2, 3, 6 (end of first dwell), and 24 h after the administration of IP cefazolin. Any urine produced was collected over the 24-h study period. A validated HPLC method was used to analyze cefazolin in plasma, dialysate, and urine. The bioavailability was found to be 77.9 ± 3.1%, volume of distribution 0.20 ± 0.05 L/kg, and plasma half-life 39.9 ± 25.4 h. Mean total, renal, and peritoneal clearances were 4.5 ± 2.3, 1.4 ± 1.1, and 3.5 ± 1.8 ml/min, respectively. Mean plasma and dialysate concentrations at 24 h were 42.8 ± 14.3 and 31.8 ± 11.7 mcg/ml, respectively, well above the minimum inhibitory concentrations (MIC) of susceptible organisms. A once daily IP cefazolin dose of 500 mg/L gave desirable pharmacokinetic attributes for use as a suitable alternative to vancomycin for empiric treatment of CAPD-associated peritonitis.

scholarly journals hCGbeta core fragment is a metabolite of hCG: evidence from infusion of recombinant hCG

2000 ◽  
Vol 164 (3) ◽  
pp. 299-305 ◽  
Author(s):  
RJ Norman ◽  
MM Buchholz ◽  
AA Somogyi ◽  
F Amato
Keyword(s):  
Renal Clearance ◽  
Clearance Rate ◽  
Half Life ◽  
Urine Samples ◽  
Molar Ratio ◽  
Gel Chromatography ◽  
Core Fragment ◽  
Terminal Half Life ◽  
Intact Molecule ◽  
The Mean

The availability of recombinant human chorionic gonadotrophin (r-hCG) has allowed us to measure its metabolic and renal clearance rates and to study the origin of the beta core fragment of hCG (hCGbetacf). Serum and urine samples were collected from six subjects, after an intravenous injection of 2 mg (equivalent to 44 000 IU Urinary hCG) r-hCG, and assayed for hCG and the beta subunit (hCGbeta). Urine from four of the subjects was also subjected to gel chromatography and assayed for hCGbetacf and hCG. r-hCG, administered as an intravenous dose, was distributed, initially in a volume of 3.4+/-0.7 l (mean+/-s.d.) and then in 6.5+/-1.15 l at steady-state. The disappearance of r-hCG from serum was bi-exponential, with an initial half-life of 4.5+/-0.7 h and a terminal half-life of 29.0+/-4.6 h. The mean residence time was 28. 6+/- 3.6 h and the total systemic clearance rate of r-hCG was 226+/-18 ml/h. The renal clearance rate was 28.75+/-6.2 ml/h (mean+/-s.d). hCGbetacf was detected in all urine samples collected at 6 h intervals. Over the 138 h period of urine collection, 12.9% (range 10.1-17.3% ) of r-hCG injected was recovered as the intact molecule and 1.7% (range 0.8-2.9%) was recovered as the hCGbetacf, in 4 subjects. The molar ratio of hCGbetacf to hCG in urine increased from 3.1+/-1.7%, on day 1, to 76+/-34.3% (mean+/-s.e.m.) on day 5, after r-hCG infusion, suggesting that hCGbetacf is a metabolic product of the infused r-hCG.

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