scholarly journals Complete Oral Clearance

2020 ◽  
Author(s):  
Keyword(s):  
Oral Clearance

scholarly journals Pharmacokinetics of Lopinavir-Ritonavir with and without Nonnucleoside Reverse Transcriptase Inhibitors in Ugandan HIV-Infected Adults

2010 ◽  
Vol 54 (7) ◽  
pp. 2965-2973 ◽  
Author(s):  
C. Kityo ◽  
A. S. Walker ◽  
L. Dickinson ◽  
F. Lutwama ◽  
J. Kayiwa ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Geometric Mean ◽  
Oral Clearance ◽  
Reverse Transcriptase Inhibitors ◽  
Time Curve ◽  
Nonnucleoside Reverse Transcriptase Inhibitors ◽  
Concentration Time ◽  
Half Dose ◽  
Trial Participants ◽  
Dose Tablet

ABSTRACT We evaluated the pharmacokinetics of lopinavir-ritonavir with and without nonnucleoside reverse transcriptase inhibitors (NNRTIs) in Ugandan adults. The study design was a three-period crossover study (3 tablets [600 mg of lopinavir/150 mg of ritonavir {600/150 mg}], 4 capsules [533/133 mg], and 2 tablets [400/100 mg] twice a day [BD]; n = 40) of lopinavir-ritonavir with NNRTIs and a parallel one-period study (2 tablets BD; n = 20) without NNRTIs. Six-point pharmacokinetic sampling (0, 2, 4, 6, 8, and 12 h) was undertaken after observed intake with a standardized breakfast. Ugandan DART trial participants receiving efavirenz (n = 20), nevirapine (n = 18), and no NNRTI (n = 20) had median ages of 41, 35, and 37 years, respectively, and median weights of 60, 64, and 63 kg, respectively. For the no-NNRTI group, the geometric mean (percent coefficient of variation [%CV]) lopinavir area under the concentration-time curve from 0 to 12 h (AUC0-12) was 110.1 (34%) μg·h/liter. For efavirenz, the geometric mean lopinavir AUC0-12 (%CV) values were 91.8 μg·h/liter (58%), 65.7 μg·h/liter (39%), and 54.0 μg·h/liter (65%) with 3 tablets, 4 capsules, and 2 tablets BD, respectively, with corresponding (within-individual) geometric mean ratios (GMR) for 3 and 2 tablets versus 4 capsules of 1.40 (90% confidence interval [CI], 1.18 to 1.65; P = 0.002) and 0.82 (90% CI, 0.68 to 0.99; P = 0.09), respectively, and the apparent oral clearance (CL/F) values were reduced by 58% and 1%, respectively. For nevirapine, the geometric mean lopinavir AUC0-12 (%CV) values were 112.9 μg·h/liter (30%), 68.1 μg·h/liter (53%), and 61.5 μg·h/liter (52%), respectively, with corresponding GMR values of 1.66 (90% CI, 1.46 to 1.88; P < 0.001) and 0.90 (90% CI, 0.77 to 1.06; P = 0.27), respectively, and the CL/F was reduced by 57% and 7%, respectively. Higher values for the lopinavir concentration at 12 h (C 12) were observed with 3 tablets and efavirenz-nevirapine (P = 0.04 and P = 0.0005, respectively), and marginally lower C 12 values were observed with 2 tablets and efavirenz-nevirapine (P = 0.08 and P = 0.26, respectively). These data suggest that 2 tablets of lopinavir-ritonavir BD may be inadequate when dosed with NNRTIs in Ugandan adults, and the dosage should be increased by the addition of an additional adult tablet or a half-dose tablet (100/25 mg), where available.

Quantitative Assessment of CYP2C9 Genetic Polymorphisms Effect on the Oral Clearance of S-Warfarin in Healthy Subjects

2016 ◽  
Vol 21 (1) ◽  
pp. 75-83 ◽  
Author(s):  
Chanan Shaul ◽  
Simcha Blotnick ◽  
Mordechai Muszkat ◽  
Meir Bialer ◽  
Yoseph Caraco
Keyword(s):  
Genetic Polymorphisms ◽  
Healthy Subjects ◽  
Quantitative Assessment ◽  
Oral Clearance

Pharmacokinetic factors affecting antidepressant drug clearance and clinical effect: evaluation of doxepin and imipramine--new data and review.

1988 ◽  
Vol 34 (5) ◽  
pp. 863-880 ◽  
Author(s):  
L Ereshefsky ◽  
T Tran-Johnson ◽  
C M Davis ◽  
A LeRoy
Keyword(s):  
Dietary Habits ◽  
Antidepressant Drug ◽  
Antidepressant Drugs ◽  
Drug Clearance ◽  
Metabolic Phenotype ◽  
Therapeutic Monitoring ◽  
Fixed Dose ◽  
Oral Clearance ◽  
Clearance Rates ◽  
Factors Affecting

Abstract The selection of a starting dose for an antidepressant, and subsequent clinical titration to an appropriate therapeutic dosage, should be based on pharmacokinetic and pharmacodynamic principles. In the past decade, therapeutic monitoring of antidepressant drugs and use of pharmacokinetic principles have been shown to be an improvement over the dose-response approach. Endogenous (e.g., genetic metabolic phenotype, hepatic blood flow, and protein binding) and exogenous factors (e.g., smoking, dietary habits, concurrent medications) are capable of influencing physiological and pharmacokinetic variables in patients, accounting for the marked interindividual differences in the clearance rates of cyclic antidepressants. Interpatient variability for steady-state concentrations in plasma (Cpss) greater than 20-fold are observed at a fixed dose of imipramine (r2 = 0.525, df = 346, t = 19.541, P less than 0.0001) or doxepin (r2 = 0.506, df = 128, t = 11.403, P less than 0.0001). Analysis of doxepin in plasma vs estimated in oral clearance for 61 patients demonstrates a significant decline in oral clearance as a function of Cpss. At doses approaching the upper range recommended for the treatment of depression, Cpss appear to approach, in at least a few individuals, the maximum metabolic capacity of the patient (Vmax), leading to greater-than-expected increases in concentrations for a given dosage increment. Significant alterations in oral clearance are observed when medications are administered concomitantly. A greater-than-threefold difference in mean oral doxepin clearance rates is observed between two groups of patients receiving additional medications that are either inducers or inhibitors (P less than 0.0001, df = 32, t = 6.687). Pharmacokinetic principles defining and explaining the determinants of oral clearance can provide the clinician with a greater insight into the reasons for therapeutic failure and toxicity.

Zalcitabine Population Pharmacokinetics: Application of Radioimmunoassay

1998 ◽  
Vol 42 (2) ◽  
pp. 409-413 ◽  
Author(s):  
John M. Adams ◽  
Mark J. Shelton ◽  
Ross G. Hewitt ◽  
Mary DeRemer ◽  
Robin DiFrancesco ◽  
...  
Keyword(s):  
Population Pharmacokinetics ◽  
Information Age ◽  
Compartment Model ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Studies ◽  
Oral Clearance ◽  
Standard Curve ◽  
Immunodeficiency Virus ◽  
Traditional Approaches

ABSTRACT Zalcitabine population pharmacokinetics were evaluated in 44 human immunodeficiency virus-infected patients (39 males and 5 females) in our immunodeficiency clinic. Eighty-one blood samples were collected during routine clinic visits for the measurement of plasma zalcitabine concentrations by radioimmunoassay (1.84 ± 1.24 samples/patient; range, 1 to 6 samples/patient). These data, along with dosing information, age (38.6 ± 7.13 years), sex, weight (79.1 ± 15.0 kg), and estimated creatinine clearance (89.1 ± 21.5 ml/min), were entered into NONMEM to obtain population estimates for zalcitabine pharmacokinetic parameters (4). The standard curve of the radioimmunoassay ranged from 0.5 to 50.0 ng/ml. The observed concentrations of zalcitabine in plasma ranged from 2.01 to 8.57 ng/ml following the administration of doses of either 0.375 or 0.75 mg. A one-compartment model best fit the data. The addition of patient covariates did not improve the basic fit of the model to the data. Oral clearance was determined to be 14.8 liters/h (0.19 liter/h/kg; coefficient of variation [CV] = 23.8%), while the volume of distribution was estimated to be 87.6 liters (1.18 liters/kg; CV = 54.0%). We were also able to obtain individual estimates of oral clearance (range, 8.05 to 19.8 liters/h; 0.11 to 0.30 liter/h/kg) and volume of distribution (range, 49.2 to 161 liters; 0.43 to 1.92 liters/kg) of zalcitabine in these patients with the POSTHOC option in NONMEM. Our value for oral clearance agrees well with other estimates of oral clearance from traditional pharmacokinetic studies of zalcitabine and suggests that population methods may be a reasonable alternative to these traditional approaches for obtaining information on the disposition of zalcitabine.

scholarly journals CYP2C19*2 Polymorphism Is Associated with Impaired Oral Clearance of Gliclazide in Healthy Chinese

2020 ◽  
Vol Volume 12 ◽  
pp. 397-401
Author(s):  
Elaine Chow ◽  
Emily Poon ◽  
Benny Siu Pong Fok ◽  
Juliana CN Chan ◽  
Brian Tomlinson
Keyword(s):  
Oral Clearance ◽  
Healthy Chinese

scholarly journals Identification of Swallowing Tasks From a Modified Barium Swallow Study That Optimize the Detection of Physiological Impairment

2017 ◽  
Vol 60 (7) ◽  
pp. 1855-1863 ◽  
Author(s):  
R. Jordan Hazelwood ◽  
Kent E. Armeson ◽  
Elizabeth G. Hill ◽  
Heather Shaw Bonilha ◽  
Bonnie Martin-Harris
Keyword(s):  
Generalized Estimating Equations ◽  
High Probability ◽  
Secondary Data ◽  
Barium Swallow ◽  
Oral Clearance ◽  
Airway Protection ◽  
Modified Barium Swallow ◽  
Severe Impairment ◽  
Swallow Study ◽  
Modified Barium Swallow Study

Purpose The purpose of this study was to identify which swallowing task(s) yielded the worst performance during a standardized modified barium swallow study (MBSS) in order to optimize the detection of swallowing impairment. Method This secondary data analysis of adult MBSSs estimated the probability of each swallowing task yielding the derived Modified Barium Swallow Impairment Profile (MBSImP™©; Martin-Harris et al., 2008) Overall Impression (OI; worst) scores using generalized estimating equations. The range of probabilities across swallowing tasks was calculated to discern which swallowing task(s) yielded the worst performance. Results Large-volume, thin-liquid swallowing tasks had the highest probabilities of yielding the OI scores for oral containment and airway protection. The cookie swallowing task was most likely to yield OI scores for oral clearance. Several swallowing tasks had nearly equal probabilities (≤ .20) of yielding the OI score. Conclusions The MBSS must represent impairment while requiring boluses that challenge the swallowing system. No single swallowing task had a sufficiently high probability to yield the identification of the worst score for each physiological component. Omission of swallowing tasks will likely fail to capture the most severe impairment for physiological components critical for safe and efficient swallowing. Results provide further support for standardized, well-tested protocols during MBSS.

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