Plasma Concentrations of Radiocalcium after Oral Administration, and Their Relationship to Absorption

1970 ◽  
Vol 38 (1) ◽  
pp. 27-39 ◽  
Author(s):  
P. Tothill ◽  
A. W. Dellipiani ◽  
J. Calvert
Keyword(s):  
Plasma Concentration ◽  
Oral Dose ◽  
Plasma Clearance ◽  
Calcium Absorption ◽  
Plasma Concentrations ◽  
Total Absorption ◽  
Isotope Method ◽  
Exchange Processes ◽  
Disappearance Curve ◽  
Double Isotope

1. Different radioisotopes of calcium were administered orally and intravenously to a series of patients, some normal and others with diseases that might affect calcium absorption or metabolism. Concentrations of the two isotopes in plasma were determined at intervals. A mathematical procedure was developed for deriving from these measurements the total absorption of the oral dose and also the absorption/time relationship. 2. The correlation between absorption and plasma concentration of the oral dose at various times after administration was studied and found to be very good, the 2 hr plasma level giving the best correlation, particularly when account was taken of the patient's weight. 3. The effect of variations in the disappearance curve of the injected isotope upon the shape of the plasma appearance curve of the oral isotope was examined. It is concluded that for the majority of cases, when absorption is not greatly delayed, and the exchange processes determining the shape of the disappearance curve are not markedly abnormal, 2 hr plasma concentration gives a good indication of absorption. When abnormalities in these processes are present, only the double isotope method gives accurate results. 4. The results were applied to examine the validity of other published methods of analysis. It was found that plasma concentrations of orally administered radiocalcium alone can give useful information about absorption, but not about plasma clearance.

The Bioavailability of Orphenadrine Hydrochloride after Intramuscular and Oral Administration

1982 ◽  
Vol 10 (6) ◽  
pp. 447-450 ◽  
Author(s):  
G Rutigliano ◽  
J J M Labout
Keyword(s):  
Plasma Concentration ◽  
Oral Dose ◽  
Oral Administration ◽  
Intramuscular Injection ◽  
Dosage Form ◽  
Plasma Concentrations ◽  
Clinical Use ◽  
Unchanged Drug ◽  
Single Intramuscular Injection ◽  
Oral Doses

The bioavailability of orphenadrine hydrochloride after a single intramuscular injection was compared to that after a single oral dose by following serial plasma concentration estimations of the unchanged drug. The bioavailability of orphenadrine from the intramuscular dosage form proved to be equal to or even greater than that from the tablet. Eight subjects received 40 mg orphenadrine HCl intramuscularly and 50 mg orally on separate occasions 1 week apart. The first hour plasma concentrations after intramuscular doses were significantly higher than those after oral doses, supporting the clinical use of the intramuscular route in those indications where rapid effects of the drug are required.

The Reproducibility of Double-Isotope Deconvolution Measurements of Intestinal Calcium Absorption

1980 ◽  
Vol 59 (3) ◽  
pp. 169-172 ◽  
Author(s):  
Marisol Tellez ◽  
J. Reeve ◽  
J. P. Royston ◽  
N. Veall ◽  
R. Wootton
Keyword(s):  
Absorption Rate ◽  
Calcium Absorption ◽  
Mean Transit Time ◽  
Maximum Absorption ◽  
Single Measurement ◽  
Isotope Method ◽  
Individual Variations ◽  
Double Isotope ◽  
Test Result ◽  
Fractional Absorption

1. Radiocalcium absorption was measured in duplicate in 10 subjects by the double-isotope method, with calcium as the oral carrier (2.5 mmol). Analysis of variance gave 95% confidence limits for a single measurement of fractional absorption and maximum absorption rate in a given individual of ±16.5% of administered dose and ±18.2% of dose/h respectively. 2. The size of these within individual variations suggests that alterations in the rate of calcium absorption-5-contribute to the week-to-week stabilization of some other controlled variable, such as plasma concentration of calcium. 3. In six of the subjects, calcium absorption was also measured with calcium loads at concentrations of 0.5, 5.0 and 20 mmol. Significant falls in fractional absorption, maximum absorption rate and mean transfer rate occurred as the load increased, together with a rise in mean transit time. Although between-individual differences at a given load were considerable, given a single-test result with a known carrier load, it is possible to predict quite accurately the results which would be obtained if a different carrier load were to be given.

EFFECT OF HEPARIN ON THE CORTICOSTERONE SECRETION RATE WITH A DESCRIPTION OF THE DOUBLE ISOTOPE METHOD USED

1967 ◽  
Vol 56 (1_Suppl) ◽  
pp. S140 ◽  
Author(s):  
A. F. Casparie ◽  
Th. J. Benraad ◽  
P. W. C. Kloppenborg ◽  
C. L. H. Majoor
Keyword(s):  
Secretion Rate ◽  
Isotope Method ◽  
Corticosterone Secretion ◽  
Double Isotope

Clinical Impact of Co-medication of Levetiracetam and Clobazam with Proton Pump Inhibitors: A Drug Interaction Study

2020 ◽  
Vol 21 (2) ◽  
pp. 126-131
Author(s):  
Bhuvanachandra Pasupuleti ◽  
Vamshikrishna Gone ◽  
Ravali Baddam ◽  
Raj Kumar Venisetty ◽  
Om Prakash Prasad
Keyword(s):  
Plasma Concentration ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Plasma Concentrations ◽  
Control Group ◽  
Drug Concentrations ◽  
Significant Difference ◽  
Post Hoc ◽  
Hydrolysis Of ◽  
Cytochrome P 450

Background: Clobazam (CLBZ) metabolized primarily by Cytochrome P-450 isoenzyme CYP3A4 than with CYP2C19, Whereas Levetiracetam (LEV) is metabolized by hydrolysis of the acetamide group. Few CYP enzymes are inhibited by Proton Pump Inhibitors (PPIs) Pantoprazole, Esomeprazole, and Rabeprazole in different extents that could affect drug concentrations in blood. The aim of the present study was to evaluate the effect of these PPIs on the plasma concentrations of LEV and CLBZ. Methods: Blood samples from 542 patients were included out of which 343 were male and 199 were female patients and were categorized as control and test. Plasma samples analyzed using an HPLC-UV method. Plasma concentrations were measured and compared to those treated and those not treated with PPIs. One way ANOVA and games Howell post hoc test used by SPSS 20 software. Results: CLBZ concentrations were significantly 10 folds higher in patients treated with Pantoprazole (P=0.000) and 07 folds higher in patients treated with Esmoprazole and Rabeprazole (P=0.00). Whereas plasma concentration of LEV control group has no statistical and significant difference when compared to pantoprazole (P=0.546) and with rabeprazole and esomeprazole was P=0.999. Conclusion: The effect of comedication with PPIs on the plasma concentration of clobazam is more pronounced for pantoprazole to a greater extent when compared to esomeprazole and rabeprazole. When pantoprazole is used in combination with clobazam, dose reduction of clobazam should be considered, or significance of PPIs is seen to avoid adverse effects.

Design, Synthesis, and Pharmacokinetic Evaluation of O-Carbamoyl Tizoxanide Prodrugs

2020 ◽  
Vol 16 ◽  
Author(s):  
Xi He ◽  
Wenjun Hu ◽  
Fanhua Meng ◽  
Xingzhou Li
Keyword(s):  
Plasma Concentration ◽  
Broad Spectrum ◽  
Plasma Concentrations ◽  
Antiviral Drug ◽  
Systemic Exposure ◽  
Pharmacokinetic Profile ◽  
Hydroxyl Group ◽  
First Pass

Background: The broad-spectrum antiparasitic drug nitazoxanide (N) has been repositioned as a broad-spectrum antiviral drug. Nitazoxanide’s in vivo antiviral activities are mainly attributed to its metabolitetizoxanide, the deacetylation product of nitazoxanide. In reference to the pharmacokinetic profile of nitazoxanide, we proposed the hypotheses that the low plasma concentrations and the low system exposure of tizoxanide after dosing with nitazoxanide result from significant first pass effects in the liver. It was thought that this may be due to the unstable acyloxy bond of nitazoxanide. Objective: Tizoxanide prodrugs, with the more stable formamyl substituent attached to the hydroxyl group rather than the acetyl group of nitazoxanide, were designed with the thought that they might be more stable in plasma. It was anticipated that these prodrugs might be less affected by the first pass effect, which would improve plasma concentrations and system exposure of tizoxanide. Method: These O-carbamoyl tizoxanide prodrugs were synthesized and evaluated in a mouse model for pharmacokinetic (PK) properties and in an in vitro model for plasma stabilities. Results: The results indicated that the plasma concentration and the systemic exposure of tizoxanide (T) after oral administration of O-carbamoyl tizoxanide prodrugs were much greater than that produced by equimolar dosage of nitazoxanide. It was also found that the plasma concentration and the systemic exposure of tizoxanide glucuronide (TG) were much lower than that produced by nitazoxanide. Conclusion: Further analysis showed that the suitable plasma stability of O-carbamoyl tizoxanide prodrugs is the key factor in maximizing the plasma concentration and the systemic exposure of the active ingredient tizoxanide.

scholarly journals Oral absorption and drug interaction kinetics of moxifloxacin in an animal model of weightlessness

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Dong Liang ◽  
Jing Ma ◽  
Bo Wei
Keyword(s):  
Oral Dose ◽  
Oral Absorption ◽  
Jugular Vein ◽  
Plasma Concentrations ◽  
Pharmacokinetic Data ◽  
Simulated Weightlessness ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Interaction Kinetics ◽  
Kinetics Of

AbstractTo investigate the effect of simulated weightlessness on the pharmacokinetics of orally administered moxifloxacin and the antacid Maalox or the antidiarrheal Pepto-Bismol using a tail-suspended (TS) rat model of microgravity. Fasted control and TS, jugular-vein-cannulated, male Sprague-Dawley rats received either a single 5 mg/kg intravenous dose or a single 10 mg/kg oral dose of moxifloxacin alone or with a 0.625 mL/kg oral dose of Maalox or a 1.43 mL/kg oral dose of Pepto-Bismol. Plasma concentrations of moxifloxacin were measured by HPLC. Pharmacokinetic data were analyzed using WinNonlin. Simulated weightlessness had no effect on moxifloxacin disposition after intravenous administration but significantly decreased the extent of moxifloxacin oral absorption. The coadministration of moxifloxacin with Maalox to either control or TS rats caused significant reductions in the rate and extent of moxifloxacin absorption. In contrast, the coadministration of moxifloxacin with Pepto-Bismol to TS rats had no significant effect on either the rate or the extent of moxifloxacin absorption. These interactions showed dose staggering when oral administrations of Pepto-Bismol and moxifloxacin were separated by 60 min in control rats but not in TS rats. Dose staggering was more apparent after the coadministration of Maalox and moxifloxacin in TS rats.

scholarly journals Physiologically Based Pharmacokinetic Models of Probenecid and Furosemide to Predict Transporter Mediated Drug-Drug Interactions

2020 ◽  
Vol 37 (12) ◽  
Author(s):  
Hannah Britz ◽  
Nina Hanke ◽  
Mitchell E. Taub ◽  
Ting Wang ◽  
Bhagwat Prasad ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Organic Anion ◽  
Plasma Concentrations ◽  
Whole Body ◽  
Time Profiles ◽  
Pbpk Models ◽  
Physiologically Based Pharmacokinetic ◽  
Concentration Time ◽  
Anion Transporter ◽  
Physiologically Based

Abstract Purpose To provide whole-body physiologically based pharmacokinetic (PBPK) models of the potent clinical organic anion transporter (OAT) inhibitor probenecid and the clinical OAT victim drug furosemide for their application in transporter-based drug-drug interaction (DDI) modeling. Methods PBPK models of probenecid and furosemide were developed in PK-Sim®. Drug-dependent parameters and plasma concentration-time profiles following intravenous and oral probenecid and furosemide administration were gathered from literature and used for model development. For model evaluation, plasma concentration-time profiles, areas under the plasma concentration–time curve (AUC) and peak plasma concentrations (Cmax) were predicted and compared to observed data. In addition, the models were applied to predict the outcome of clinical DDI studies. Results The developed models accurately describe the reported plasma concentrations of 27 clinical probenecid studies and of 42 studies using furosemide. Furthermore, application of these models to predict the probenecid-furosemide and probenecid-rifampicin DDIs demonstrates their good performance, with 6/7 of the predicted DDI AUC ratios and 4/5 of the predicted DDI Cmax ratios within 1.25-fold of the observed values, and all predicted DDI AUC and Cmax ratios within 2.0-fold. Conclusions Whole-body PBPK models of probenecid and furosemide were built and evaluated, providing useful tools to support the investigation of transporter mediated DDIs.

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