Statistical Modeling of Pharmacokinetic Systems

1976 ◽  
Vol 98 (1) ◽  
pp. 37-43 ◽  
Author(s):  
J. O. Tsokos ◽  
C. P. Tsokos
Keyword(s):  
Oral Administration ◽  
Drug Concentration ◽  
Rate Constants ◽  
Pharmacokinetic Model ◽  
Compartmental Model ◽  
Statistical Treatment ◽  
Numerical Comparison ◽  
The Mean ◽  
Intravenous And Oral Administration ◽  
Initial Drug

A statistical treatment of a pharmacokinetic compartmental model is described, wherein the initial drug concentration and/or the rate constants governing the distribution of the drug between the appropriate compartments are considered to be random variables. A specific pharmacokinetic model which describes the profile of the antibiotic coumermycin A, following intravenous and oral administration in man, is stochastized and a numerical comparison between the deterministic and the mean of the random solutions as a function of time is presented.

scholarly journals Pharmacokinetics of oral and intravenous ofloxacin in children with multidrug-resistant typhoid fever.

1996 ◽  
Vol 40 (9) ◽  
pp. 2167-2172 ◽  
Author(s):  
D B Bethell ◽  
N P Day ◽  
N M Dung ◽  
C McMullin ◽  
H T Loan ◽  
...  
Keyword(s):  
Oral Administration ◽  
Typhoid Fever ◽  
Apparent Volume ◽  
Salmonella Typhi ◽  
Multidrug Resistant ◽  
Volume Of Distribution ◽  
Systemic Clearance ◽  
Time To Peak ◽  
The Mean ◽  
Intravenous And Oral Administration

The pharmacokinetics of oral and intravenous ofloxacin (7.5 mg.kg of body weight-1 given over 30 min) were studied in an open crossover study of 17 Vietnamese children, aged between 5 and 14 years, with acute uncomplicated typhoid fever. Following oral administration, the median (95% confidence interval [CI]) time to peak concentration of ofloxacin in serum (Cmax) was 1.7 h (1.4 to 1.9 h) and the mean (95% CI) Cmax was 5.5 mg.liter-1 (4.7 to 6.3 mg.liter-1) compared with a Cmax of 8.7 mg.liter-1 (7.6 to 9.7 mg.liter-1) following the intravenous infusion. The median (95% CI) total apparent volume of distribution following the first intravenous dose, 1.35 liter.kg-1 (1.17 to 1.73 liter.kg-1), was significantly larger than that following the second dose, 0.99 liter.kg-1 (0.86 to 1.17 liter.kg-1; P < 0.0005), although the estimates for systemic clearance were similar: 0.255 liter.kg-1 h-1 (0.147 to 0.325 liter.kg-1 h-1) compared with 0.172 liter.kg-1 h-1 (0.127 to 0.292 liter.kg-1 h-1; P = 0.14). The mean residence times (95% CI) following intravenous and oral administration were similar: 5.24 h (4.84 to 6.58 h) and 6.24 h (5.32 to 7.85 h), respectively. The mean (95% CI) oral bioavailability was 91% (74 to 109%). The peak concentrations in serum were 10 to 100 times higher than the maximum MICs for ofloxacin against multidrug-resistant Salmonella typhi isolated in this area. Although the systemic clearance values were higher than those reported previously for adults, these data overall suggest that weight-or area-adjusted dose regimens for the treatment of typhoid in older children should be the same as those for adults.

Pharmacokinetic Comparison of Intravenous and Oral Chloramphenicol in Patients with Haemophilus in fluenzae Meningitis

PEDIATRICS ◽  
1981 ◽  
Vol 67 (5) ◽  
pp. 656-660
Author(s):  
Ram Yogev ◽  
William M. Kolling ◽  
Tommy Williams
Keyword(s):  
Serum Level ◽  
Oral Administration ◽  
Intravenous Administration ◽  
Half Life ◽  
Peak Serum ◽  
Peak Serum Level ◽  
Wide Range ◽  
Csf Levels ◽  
The Mean ◽  
Intravenous And Oral Administration

The pharmacokinetics of chloramphenicol following intravenous and oral administration were studied in 14 infants with Haemophilus influenzae meningitis. Following five days of treatment with intravenous chloramphenicol (100 mg/kg/day every six hours), oral chloramphenicol was substituted at the same dose. Multiple serum levels of chloramphenicol were determined after an intravenous dose on day 4 and after an oral dose on day 10. CSF levels were measured six hours after intravenous or oral chloramphenicol dose on those days (CSF trough). Following intravenous administration, the mean peak serum level of 15.0 µ/g ml was reached at 45 minutes. In comparison, after oral chloramphenicol in the same dosage, the mean peak serum level of 18.5 µg ml was achieved at two to three hours. The mean serum half-life of the drug (6.5 hours) was significantly longer after oral administration than after intravenous chloramphenicol (4.0 hours) (P .001). The increased serum half-life following orally administered chloramphenicol was occasionally associated with drug accumulation. In addition, mean trough CSF levels were somewhat higher when the patient received oral medication (6.6 µg/ml) compared to intravenous administration (4.2 µ/ml) (P .001). For any treatment regimen for H influenzae meningitis that includes a period of oral chloramphenicol therapy the patient should be hospitalized to ensure compliance. Because of the wide range of individual variation in serum half-life that may result in accumulation, periodic monitoring of serum chloramphenicol levels is also recommended.

scholarly journals Serum and Cerebrospinal Fluid Pharmacokinetics of Intravenous and Oral Lamivudine in Human Immunodeficiency Virus-Infected Children

1998 ◽  
Vol 42 (12) ◽  
pp. 3187-3192 ◽  
Author(s):  
Brigitta U. Mueller ◽  
Linda L. Lewis ◽  
Geoffrey J. Yuen ◽  
Maureen Farley ◽  
Amy Keller ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cerebrospinal Fluid ◽  
Body Weight ◽  
Oral Administration ◽  
Drug Concentration ◽  
Serum Drug Concentration ◽  
Time Curve ◽  
Concentration Time ◽  
Immunodeficiency Virus ◽  
The Mean

ABSTRACT We studied the pharmacokinetics of intravenously and orally administered lamivudine at six dose levels ranging from 0.5 to 10 mg/kg of body weight in 52 children with human immunodeficiency virus infection. A two-compartment model with first-order elimination from the central compartment was simultaneously fitted to the serum drug concentration-time data obtained after intravenous and oral administration. The maximal concentration at the end of the 1-h intravenous infusion and the area under the concentration-time curve after oral and intravenous administration increased proportionally with the dose. The mean clearance of lamivudine (± standard deviation) in the children was 0.53 ± 0.19 liter/kg/h (229 ± 77 ml/min/m2 of body surface area), and the mean half-lives at the distribution and elimination phases were 0.23 ± 0.18 and 2.2 ± 2.1 h, respectively. Clearance was age dependent when normalized to body weight but age independent when normalized to body surface area. Lamivudine was rapidly absorbed after oral administration, and 66% ± 25% of the oral dose was absorbed. Serum lamivudine concentrations were maintained above 1 μM for ≥8 h of 24 h on the twice daily oral dosing schedule with doses of ≥2 mg/kg. The cerebrospinal fluid drug concentration measured 2 to 4 h after the dose was 12% (range, 0 to 46%) of the simultaneously measured serum drug concentration. A limited-sampling strategy was developed to estimate the area under the concentration-time curve for concentrations in serum at 2 and 6 h.

scholarly journals Saliva and Serum Lithium Monitoring in Hospitalized Patients and Possibility to Replace Serum to Saliva

2008 ◽  
Vol 6 (4) ◽  
pp. 32-35 ◽  
Author(s):  
Nafija Serdarević ◽  
Franc Kozjek ◽  
Ivan Malešič
Keyword(s):  
Oral Administration ◽  
Pharmacokinetic Model ◽  
Absorption Spectrometry ◽  
Lithium Carbonate ◽  
Lithium Ions ◽  
Elimination Half ◽  
The Mean ◽  
Student Test ◽  
High Level

The lithium ions concentration in human serum and saliva was determined using dry-slide technology Vitros 250 Analyser (Ortho Clinical Diagnostic) and atomic absorption spectrometry Perkin Elmer 403 (AAS). We analyzed lithium ions in 100 serum and saliva specimens of patients after oral administration of lithium carbonate (3 x 300 mg) Jadran, Galen Laboratory Rijeka. Saliva and blood were taken 2 and 12 hours after the last dose. At the same time lithium ions at samples of blood and saliva were determined with both methods which showed high level of correlation. The mean difference of lithium ions between saliva and serum was statistically significant for p<0.05 using t student test. At saliva we got constant of elimination Kel = 0.02(-1)h and elimination half life (t(1/2)) was t(1/2)=34.6 h. For serum was t(1/2)= 24 h what means that lithium ions elimination is slower from saliva then from serum. That is the reason why probably concentration at saliva is higher then at serum. Lithium elimination is two compartment pharmacokinetic model where important part of compartment are saliva and salivary glands. At a certain point in medical treatment it could be expected to use controlled determination of lithium ions in saliva with serum as control.

scholarly journals Effects of Diabetes Mellitus Induced by Alloxan on the Pharmacokinetics of Metformin in Rats: Restoration of Pharmacokinetic Parameters to the Control State by Insulin Treatment

2008 ◽  
Vol 11 (1) ◽  
pp. 88 ◽  
Author(s):  
Myung G. Lee ◽  
Young H Choi ◽  
Inchul Lee
Keyword(s):  
Diabetes Mellitus ◽  
Oral Administration ◽  
Protein Expression ◽  
Intravenous Administration ◽  
Insulin Treatment ◽  
Pharmacokinetic Parameters ◽  
Mrna Levels ◽  
Altered Pharmacokinetic ◽  
Intravenous And Oral Administration ◽  
Control State

To test the effect of insulin treatment on the pharmacokinetics of metformin in rats with diabetes mellitus induced by alloxan (DMIA rats). The following results were reported from other studies. Metformin was metabolized via hepatic CYP2C11, 2D1, and 3A1/2 in rats. In DMIA rats, the protein expression and mRNA levels of hepatic CYP2C11 and 3A1/2 decreased and increased, respectively. In rat model of diabetes mellitus induced by streptozotocin, the protein expression of hepatic CYP2D1 was not changed. The increase in hepatic CYP1A2, 2B1, and 2E1, and decrease in hepatic CYP2C11 in DMIA rats was returned to the controls by insulin treatment. METHODS. Metformin (100 mg/kg) was administered intravenously and orally to the control rats, DMIA rats, and DMIA rats with insulin treatment for 3 weeks (DMIA rats with insulin). RESULTS. After intravenous administration of metformin to the DMIA rats, the CLR and CLNR of the drug were significantly slower than the controls. After oral administration of metformin to the DMIA rats, the AUC of the drug was also significantly greater than the controls. After intravenous administration of metformin to the DMIA rats with insulin, the significantly slower CLNR of the drug in the DMIA rats was returned to the controls. The altered pharmacokinetic indices observed following intravenous and oral administration of metformin to DMIA rats returned to the control values in the DMIA rats with insulin. CONCLUSIONS. The significantly slower CLNR of metformin in the DMIA rats could be due to the decrease in hepatic CYP2C11 than the controls. The comparable CLNR of metformin between the DMIA rats with insulin and the control rats could be due to restoration of hepatic CYP enzyme changes in DMIA rats to the controls.

Phenylbutazone blood and urine concentrations, pharmacokinetics, and effects on biomarkers of inflammation in horses following intravenous and oral administration of clinical doses

2018 ◽  
Vol 11 (6) ◽  
pp. 792-803 ◽  
Author(s):  
Heather K. Knych ◽  
Rick M. Arthur ◽  
Dan S. McKemie ◽  
Kelsey Seminoff ◽  
Briana Hamamoto‐Hardman ◽  
...  
Keyword(s):  
Oral Administration ◽  
Urine Concentrations ◽  
Intravenous And Oral Administration

EFFECT OF ETHINYLOESTRADIOL ON PLASMA TESTOSTERONE LEVELS AND URINARY TESTOSTERONE EXCRETION IN MAN

1965 ◽  
Vol 50 (1) ◽  
pp. 51-54 ◽  
Author(s):  
Enrico Forchielli ◽  
Govind S. Rao ◽  
Inder R. Sarda ◽  
Norman B. Gibree ◽  
Peter E. Pochi ◽  
...  
Keyword(s):  
Oral Administration ◽  
Plasma Testosterone ◽  
Testosterone Levels ◽  
The Mean ◽  
Normal Men ◽  
Daily Oral Administration

ABSTRACT The daily oral administration of one mg of ethinyloestradiol to normal men decreased the mean plasma testosterone from 0.84 ± 0.07 μg per 100 ml to 0.20 ± 0.04 in 21 trials and decreased the urinary testosterone from 63 ± 1.1 μg per day to 8 ± 0.3 in 16 trials.

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