Toxicokinetics of Colchicine in Humans: Analysis of Tissue, Plasma and Urine Data in Ten Cases

1992 ◽  
Vol 11 (6) ◽  
pp. 510-516 ◽  
Author(s):  
M. Rochdi ◽  
A. Sabouraud ◽  
F.J. Baud ◽  
C. Bismuth ◽  
J.M. Scherrmann
Keyword(s):  
Apparent Volume ◽  
Volume Of Distribution ◽  
Pharmacokinetic Analysis ◽  
Post Mortem ◽  
Elimination Half ◽  
High Concentrations ◽  
Human Poisoning ◽  
Total Body ◽  
Therapeutic Doses ◽  
Kinetics Of

1 A specific and sensitive radioimmunoassay was used to study the toxicokinetics of colchicine in seven cases of acute human poisoning. Post-mortem tissue concentrations of colchicine were measured in three further cases. Depending on the time of patient admission, two disposition processes could be observed. The first, in three patients, admitted early, showed a bi-exponential plasma colchicine decrease, with distribution half-lives of 30, 45 and 90 min. The second, in four patients, admitted late, showed a mono-exponential decrease. Plasma terminal half-lives ranged from 10.6 to 31.7 h for both groups. 2 Pharmacokinetic analysis of urine colchicine data was performed for two patients. The fraction of unchanged colchicine excreted in urine was about 30%, renal clearance was about 131 h-1 and three-fold less than total body clearance (391 h-1). The apparent volume of distribution was 211 kg-1. 3 Post-mortem tissue analysis showed an ubiquitous colchicine distribution. Colchicine accumulated at high concentrations in the bone marrow (more than 600 ng g-1), testicle (400 ng g-1), spleen (250 ng g-1), kidney (200 ng g-1), lung (200 ng g-1) and heart (95 ng g -1); it was also found in the brain (125 ng g-1). 4 This toxicokinetic study shows that after massive ingestion, the disposition parameters and kinetics of colchicine are not markedly modified from those occuring in healthy volunteers. The absorption process was not delayed and the distribution and elimination half-lives were in the range known to occur with therapeutic doses.

Toxicokinetics of Paraquat in Humans

1990 ◽  
Vol 9 (1) ◽  
pp. 5-12 ◽  
Author(s):  
P. Houzé ◽  
F.J. Baud ◽  
R. Mouy ◽  
C. Bismuth ◽  
R. Bourdon ◽  
...  
Keyword(s):  
Half Life ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Pharmacokinetic Analysis ◽  
Elimination Phase ◽  
Specific Radioimmunoassay ◽  
Elimination Half ◽  
Distribution Phase ◽  
Human Poisoning ◽  
Apparent Volume Of Distribution

1 The toxicokinetics of paraquat were studied in 18 cases of acute human poisoning using a specific radioimmunoassay. Plasma paraquat concentration exhibited a mean distribution half-life ( t½ α) of 5 h and a mean elimination half-life ( t½ β) of 84 h. Cardiovascular collapse supervened early during the course of the intoxication and was associated with the distribution phase. Death related to pulmonary fibrosis occurred late and was associated with the elimination phase. 2 Pharmacokinetic analysis of urine paraquat excretion confirmed the biphasic decline of paraquat. Moreover, renal paraquat and creatinine clearances were not correlated but renal paraquat clearance was never higher than the renal creatinine clearance. 3 Tissue paraquat distribution was ubiquitous with an apparent volume of distribution ranging from 1.2 to 1.6 l/kg. Muscle could represent an important reservoir explaining the long persistence of paraquat in plasma and urine for several weeks or months after poisoning.

Individualization of Theophylline Dosage in Adults with Bronchial Asthma

1986 ◽  
Vol 20 (9) ◽  
pp. 704-707 ◽  
Author(s):  
Maria J. Otero ◽  
Miguel Barrueco ◽  
Eduardo L. Marino ◽  
Francisco Gomez ◽  
Alfonso Dominguez-Gil
Keyword(s):  
Elderly Patients ◽  
Bronchial Asthma ◽  
Total Body Clearance ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Dosage Regimens ◽  
Elimination Half ◽  
Total Body ◽  
Apparent Volume Of Distribution ◽  
Body Clearance

The influence of age on the disposition of theophylline was studied in 95 adult patients (nonsmokers) with bronchial asthma requiring oral theophylline therapy: 17 patients age ≥39 years, 50 patients age 40–59 years, and 28 patients < 60 years. A decrease was observed in total body clearance together with an increase in the elimination half-life of theophylline parallel to the advance in age of the patients. The apparent volume of distribution of theophylline was similar in the three groups of patients. According to the results obtained, recommendations are made regarding the dosage regimens of theophylline in elderly patients.

scholarly journals Pharmacokinetics and Metabolism of [14C]Ribavirin in Rats and Cynomolgus Monkeys

2003 ◽  
Vol 47 (4) ◽  
pp. 1395-1398 ◽  
Author(s):  
Chin-Chung Lin ◽  
Li-Tain Yeh ◽  
Trong Luu ◽  
David Lourenco ◽  
Johnson Y. N. Lau
Keyword(s):  
Oral Dose ◽  
Oral Administration ◽  
Oral Absorption ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Total Radioactivity ◽  
Cynomolgus Monkeys ◽  
Elimination Half ◽  
Extensive Metabolism ◽  
Total Body

ABSTRACT Absorption, pharmacokinetics, distribution, metabolism, and excretion of [14C]ribavirin were studied in rats (30 mg/kg of body weight) and cynomolgus monkeys (10 mg/kg) after intravenous (i.v.) and oral administration. The oral absorption and bioavailability were 83 and 59%, respectively, in rats and 87 and 55%, respectively, in monkeys. After i.v. administration, the elimination half-life (t [1/2]) was 9.9 h in rats and 130 h in monkeys and the total body clearance was 2,600 ml/h/kg in rats and 224 ml/h/kg in monkeys. The apparent volume of distribution was 11.4 liter/kg in rats and 29.4 liter/kg in monkeys. There was extensive distribution of drug-derived radioactivity into red blood cells and extensive metabolism of ribavirin in rats and a lesser degree of metabolism in monkeys. Excretion of total radioactivity in urine from rats accounted for 84% of the i.v. dose and 83% of the oral dose, whereas that from monkeys accounted for 47% of the i.v. dose and 67% of the oral dose. Several metabolites were observed in plasma and urine from both species. The amount of unchanged ribavirin in urine from both species was quite small after either i.v. or oral administration.

scholarly journals Disposition of intravenous metronidazole in Asian surgical patients.

1996 ◽  
Vol 40 (10) ◽  
pp. 2248-2251 ◽  
Author(s):  
T Y Ti ◽  
H S Lee ◽  
Y M Khoo
Keyword(s):  
Half Life ◽  
Inverse Correlation ◽  
Volume Of Distribution ◽  
Population Based ◽  
Surgical Patients ◽  
Pharmacokinetic Analysis ◽  
Elimination Half Life ◽  
Elimination Half ◽  
The Mean ◽  
Total Body

Steady-state peak and trough concentrations of metronidazole and its metabolites were measured in the sera of 54 surgical patients who were on intravenous metronidazole, 500 mg every 8 h. These patients had no significant renal or hepatic impairment. High-pressure liquid chromatography was used to determine the concentrations of metronidazole and its metabolites. The mean peak and trough metronidazole concentrations were 28.9 +/- 11.0 and 18.0 +/- 9.9 micrograms/ml, respectively. The acid metabolite was not detectable in all the blood specimens. The mean peak concentration of the hydroxy metabolite (MH) was 6.6 +/- 4.3 micrograms/ml, the mean trough concentration of MH was 6.2 +/- 4.2 micrograms/ml, and the MH concentration/metronidazole concentration ratio was 0.4 +/- 0.24. Using a population-based method for the pharmacokinetic analysis and stepwise regression between parameters and covariables (sex, age, and weight), we found that weight showed the highest correlation with the total body clearance (CL). The mean CL was 0.89 +/- 0.3 ml min-1 kg-1 (3.029 liters/h), the mean volume of distribution was 0.73 +/- 0.14 liter/kg, and the mean elimination half-life was 10.6 +/- 4.5 h. For the patients in our study, the CL was lower and the elimination half-life was longer compared with those for healthy volunteers, but the values of these parameters were comparable to those found for hospitalized patients. There was an inverse correlation between age and CL.

scholarly journals Intravascular plasma disposition and salivary secretion of closantel and rafoxanide in sheep

1999 ◽  
Vol 70 (2) ◽  
Author(s):  
G.E. Swan ◽  
H.A. Koeleman ◽  
H.S. Steyn ◽  
M.S.G. Mülders
Keyword(s):  
Pharmacokinetic Profile ◽  
Apparent Volume ◽  
Salivary Secretion ◽  
Volume Of Distribution ◽  
Large Individual ◽  
Drug Plasma ◽  
Elimination Half ◽  
Proportional Increase ◽  
Total Body ◽  
Apparent Volume Of Distribution

The plasma and salivary disposition of closantel and rafoxanide were examined following intravenous administration in adult sheep. Two studies were conducted with rafoxanide at 7.5 mg/kg and 1 with closantel using 2 doses (5 and 15 mg/kg). The pharmacokinetic profile of both drugs in plasma were best described by a 2-compartmental model with 1st-order rate constants. Plasma disposition of closantel and rafoxanide were characterised by a rapid distribution (t1/2(a) of <30 min), long elimination half-life (t1/2(b) of 17.0 + 4.0 days for closantel and 7.2 + 0.6 days for rafoxanide), small apparent volume of distribution (Vss of <0.15 ℓ/kg) and a slow rate of total body clearance (Cl of <0.01mℓ/min/kg). The area under the drug plasma concentration curve (AUC) of closantel at 5 mg/kg was nearly twice as large as that of rafoxanide at 7.5 mg/kg resulting from the slower t1/2(b) observed with closantel compared to rafoxanide. Large individual differences were observed in the rate measurements of distribution (k12, k21 and t1/2(a)), whereas the parameters of elimination (k10, t1/2(b) and Cl), were more consistent between animals. A dose proportional increase in AUC was observed for closantel administered at 5 and 15 mg/kg. A low, constant salivary concentration of closantel (mean of 0.04+0.05 mg/mℓ) and rafoxanide (mean of 0.07+0.04 mg/mℓ) was observed during the 24-h examination period after dosing.

Distribution and kinetics of amylin in humans

1998 ◽  
Vol 274 (5) ◽  
pp. E903-E908 ◽  
Author(s):  
M. Clodi ◽  
K. Thomaseth ◽  
G. Pacini ◽  
K. Hermann ◽  
A. Kautzky-Willer ◽  
...  
Keyword(s):  
Apparent Volume ◽  
Volume Of Distribution ◽  
C Peptide ◽  
Fractional Clearance ◽  
Cell Hormone ◽  
Total Body ◽  
Relationship Of ◽  
Kinetics Of ◽  
Male Subjects ◽  
Apparent Volume Of Distribution

The aim of the study was to determine the apparent volume of distribution (VTOT), total body clearance (CL), fractional clearance, and mean residence time (MRT) of the β-cell hormone amylin. We therefore performed an intravenous injection of 50 μg of human synthetic amylin (amlintide) in nine healthy male subjects during suppression of endogenous amylin release by intravenous somatostatin (0.06 μg ⋅ kg−1⋅ min−1). The plasma levels of amylin concentrations over time were analyzed using three-exponential curves. VTOTwas 173 ± 16 ml/kg and was not different from that of insulin reported in the literature (157 ml/kg). MRT was 27.7 ± 2.1 min and thus two times the reported value for insulin (14.1 min) and C-peptide (16.4 min). CL and fractional CL were 6.2 ± 0.2 ml ⋅ kg−1⋅ min−1and 0.038 ± 0.003 min−1, respectively. Fractional CL is therefore definitely lower than that reported for insulin (0.12–0.2 min−1) but is, however, in the range of that of C-peptide (0.05 min−1). In conclusion, clearance of amylin is similar to that reported for C-peptide and much slower than insulin, indicating that the commonly used molar insulin-to-amylin ratio does not reflect the correct relationship of the two peptides.

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 Medication Dosage in Overweight and Obese Children

2017 ◽  
Vol 22 (1) ◽  
pp. 81-83 ◽  
Author(s):  
Kelly L. Matson ◽  
Evan R. Horton ◽  
Amanda C. Capino ◽  
Keyword(s):  
Hepatic Clearance ◽  
Position Statement ◽  
Volume Of Distribution ◽  
Pharmacokinetic Analysis ◽  
Overweight Children ◽  
Obese Children ◽  
Patients Âgés ◽  
Adult Dose ◽  
Total Body ◽  
State Concentration

Approximately 31.8% of U.S. children ages 2 to 19 years are considered overweight or obese. This creates significant challenges to dosing medications that are primarily weight based (mg/kg) and in predicting pharmacokinetics parameters in pediatric patients. Obese individuals generally have a larger volume of distribution for lipophilic medications. Conversely, the Vd of hydrophilic medications may be increased or decreased due to increased lean body mass, blood volume, and decrease percentage of total body water. They may also experience decreased hepatic clearance secondary to fatty infiltrates of the liver. Hence, obesity may affect loading dose, dosage interval, plasma half-life, and time to reach steady-state concentration for various medications. Weight-based dosing is also a cause for potential medication errors. This position statement of the Pediatric Pharmacy Advocacy Group recommends that weight-based dosing should be used in patients ages &lt; 18 years who are &lt; 40 kg; weight-based dosing should be used in patients ≥ 40 kg, unless, unless the recommended adult dose for the specific indication is exceeded; clinicians should use pharmacokinetic analysis for adjusting medications in overweight/obese children; and research efforts continue to evaluate dosing of medications in obese/overweight children.

Vancomycin volume of distribution estimation in adults with class III obesity

2019 ◽  
Author(s):  
Ryan D Dunn ◽  
Ryan L Crass ◽  
Joseph Hong ◽  
Manjunath P Pai ◽  
Lynne C Krop
Keyword(s):  
Body Weight ◽  
Total Body Weight ◽  
Volume Of Distribution ◽  
Patient Specific ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Parameter Estimates ◽  
Class Iii ◽  
Class Iii Obesity ◽  
Total Body

Abstract Purpose To compare methods of estimating vancomycin volume of distribution (V) in adults with class III obesity. Methods A retrospective, multicenter pharmacokinetic analysis of adults treated with vancomycin and monitored through measurement of peak and trough concentrations was performed. Individual pharmacokinetic parameter estimates were obtained via maximum a posteriori Bayesian analysis. The relationship between V and body weight was assessed using linear regression. Mean bias and root-mean-square error (RMSE) were calculated to assess the precision of multiple methods of estimating V. Results Of 241 patients included in the study sample, 159 (66.0%) had a BMI of 40.0–49.9 kg/m2, and 82 (34.0%) had a BMI of ≥50.0 kg/m2. The median (5th, 95th percentile) weight of patients was 136 (103, 204) kg, and baseline characteristics were similar between BMI groups. The mean ± S.D. V was lower in patients with a BMI of 40.0–49.9 kg/m2 than in those with a BMI of ≥50.0 kg/m2 (72.4 ± 19.6 L versus 79.3 ± 20.6 L, p = 0.009); however, body size poorly predicted V in regression analyses (R2 < 0.20). A fixed estimate of V (75 L) or use of 0.52 L/kg by total body weight yielded similar bias and error in this population. Conclusion Results of the largest analysis of vancomycin V in class III obesity to date indicated that use of a fixed V value (75 L) and use of a TBW-based estimate (0.52 L/kg) for estimation of vancomycin V in patients with a BMI of ≥40.0 kg/m2 have similar bias. Two postdistribution vancomycin concentrations are needed to accurately determine patient-specific pharmacokinetic parameters, estimate AUC, and improve the precision of vancomycin dosing in this patient population.

Inhibitory effect of phenelzine on oxidative microsomal enzyme systems of rat liver

1983 ◽  
Vol 61 (5) ◽  
pp. 524-529 ◽  
Author(s):  
P. M. Bélanger ◽  
A. Atitsé-Gbeassor
Keyword(s):  
Rat Liver ◽  
Apparent Volume ◽  
Inhibitory Effect ◽  
Volume Of Distribution ◽  
Inhibitory Effects ◽  
Oxidative Reactions ◽  
Total Body ◽  
Apparent Volume Of Distribution ◽  
Cytochrome P 450 ◽  
Substrate Addition

The inhibitory effects of phenelzine on the hepatic microsomal demethylation of aminopyrine, N,N-dimethylaniline, and p-nitroanisole on the hydroxylation of aniline and on the pharmacokinetics of antipyrine were investigated in the rat. Phenelzine produced a competitive and noncompetitive inhibition of the demethylation of p-nitroanisole and N,N-dimethylaniline, respectively, but was a mixed-type inhibitor of the aminopyrine N-demethylase and aniline hydroxylase. The inhibition constant, Ki, varied between 0.06 to 0.25 mM depending on the substrate used. Preincubation of phenelzine for 30 min with the microsomal homogenate prior to substrate addition doubled its inhibitory effect. Phenelzine induced a type II spectral change when combined with oxidized cytochrome P-450 with a Ks value of 0.4 mM. The administration of one dose of 50 mg∙kg−1 of phenelzine sulfate concomitantly with 50 mg∙kg−1 of antipyrine resulted in a significant decrease of the serum elimination of antipyrine. The serum half-life, apparent volume of distribution, and total body clearance of antipyrine were modified to 3.6 h, 294.1 mL∙kg−1, and 56.8 mL∙h−1∙kg−1, respectively, from 1.5 h, 666.7 mL∙kg−1, and 312.5 mL∙h−1∙kg−1 when antipyrine was administered alone. It is concluded that the inhibitory effect of phenelzine on the microsomal oxidative reactions of rat liver is related to its interaction with cytochrome P-450.

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