scholarly journals Complexation of Z-ligustilide with hydroxypropyl-β-cyclodextrin to improve stability and oral bioavailability

2014 ◽  
Vol 64 (2) ◽  
pp. 211-222 ◽  
Author(s):  
Yapeng Lu ◽  
Siyuan Liu ◽  
Yu Zhao ◽  
Li Zhu ◽  
Shuqin Yu
Keyword(s):  
Inclusion Complex ◽  
Oral Bioavailability ◽  
Compartment Model ◽  
Plasma Drug Concentration ◽  
Absolute Bioavailability ◽  
Plasma Drug ◽  
Concentration Time ◽  
Kneading Method ◽  
Vis Spectroscopy ◽  
The Stability

Abstract To improve the stability and oral bioavailability of Z-ligustilide (LIG), the inclusion complex of LIG with hydroxypropyl- β-cyclodextrin (HP-β-CD) was prepared by the kneading method and characterized by UV-Vis spectroscopy, differential thermal analysis (DTA) and Fourier transform infrared (FTIR) spectroscopy. LIG is capable of forming an inclusion complex with HP-b-CD and the stoichiometry of the complex was 1:1. Stability of the inclusion complex against temperature and light was greatly enhanced compared to that of free LIG. Further, oral bioavailability of LIG and the inclusion complex in rats were studied and the plasma drug concentration-time curves fitted well with the non-compartment model to estimate the absolute bioavailability, which was 7.5 and 35.9 %, respectively. In conclusion, these results show that LIG/HP-β-CD complexation can be of great use for increasing the stability and biological efficacy of LIG

scholarly journals Modifications of the Method for Calculating Absolute Drug Bioavailability

2016 ◽  
Vol 19 (2) ◽  
pp. 181
Author(s):  
Wei Jiang ◽  
Juan-juan Yang ◽  
Lei Cao ◽  
Xue Xiao ◽  
Xiao-lian Shi ◽  
...  
Keyword(s):  
Intravenous Injection ◽  
Drug Concentration ◽  
Plasma Drug Concentration ◽  
The Body ◽  
Absolute Bioavailability ◽  
Plasma Drug ◽  
Drug Bioavailability ◽  
Concentration Time ◽  
Drug Concentrations ◽  
Distribution Phase

Purpose: Absolute bioavailability (F) is calculated as the ratio of the area under the plasma drug concentration-time curve (AUC) between extravascular administration and intravenous injection. However, as distribution of a drug after intravenous administration does not reach an equilibrium in the body during the distribution phase, the plasma drug concentration at this phase does not reflect the total amount of drug in the body. The goal of this paper was to analyze the insufficiencies of the method for calculating on absolute bioavailability and to propose a modification to improve the calculation. Methods: Literature reporting absolute bioavailability published during 1983-2014 was searched for ten drug candidates. Plasma drug concentrations representing the amount of drug in the body were then calculated at each time point during the distribution phase according to the plasma drug concentration-time relationship during the elimination phase. Results: The AUC values based on the distribution equilibrium drug concentrations following intravenous injection were 75%±11% of the actually measured drug concentrations in the literature. The absolute bioavailability values in the literature were 76%±12% of the actual bioavailability based on the AUCs from distribution-equilibrium drug concentrations. Conclusions: The present method underestimates the absolute drug bioavailability and should be modified to represent the data more accurately. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

scholarly journals Effect of Food on the Bioavailability of Stavudine in Subjects with Human Immunodeficiency Virus Infection

1998 ◽  
Vol 42 (9) ◽  
pp. 2295-2298 ◽  
Author(s):  
Sanjeev Kaul ◽  
Barbara Christofalo ◽  
Ralph H. Raymond ◽  
Michael B. Stewart ◽  
Catherine M. Macleod
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hiv Infection ◽  
Drug Concentration ◽  
Plasma Drug Concentration ◽  
Maximum Plasma ◽  
Fasting State ◽  
Plasma Drug ◽  
Cell Counts ◽  
Concentration Time ◽  
Immunodeficiency Virus

ABSTRACT A randomized, three-way crossover study was carried out to determine the effects of food ingestion on the pharmacokinetics of stavudine (d4T). Fifteen subjects with human immunodeficiency virus (HIV) infection and CD4+ cell counts of ≥200/μl received 70 mg of d4T in a fasting state or 1 h before or 5 min after a standardized high-fat breakfast. A 7- to 15-day washout period was included between treatments. Blood and urine were collected before and for 10 h after dosing, and plasma and urine d4T concentrations were determined with a validated radioimmunoassay. Plasma drug concentration-time data were analyzed with a noncompartmental model. The mean maximum plasma drug concentration (C max) and the time toC max (T max) for administration of d4T after a meal were significantly lower and longer (P = 0.0001 for both measures) than those observed in the fasting state, although the area under the concentration-time curve from time zero to infinity (AUC0–∞) was not significantly different. Neither of these parameters was significantly altered when d4T was taken 1 h before a meal. The bioavailability of d4T taken after a meal was 95% of that observed in the fasting state, and it was 97% when d4T was administered before a meal (P > 0.05 for both comparisons with the fasting state). The results of this study indicate that (i) ingestion of food does not affect the bioavailability of d4T and that patients with HIV infection can take it without regard to meals, and (ii) absorption is essentially complete within 1 h when d4T is administered in the fasted state.

scholarly journals Absolute Bioavailability ofcis-Mirincamycin andtrans-Mirincamycin in Healthy Rhesus Monkeys andEx VivoAntimalarial Activity against Plasmodium falciparum

2011 ◽  
Vol 55 (12) ◽  
pp. 5881-5886 ◽  
Author(s):  
Phisit Khemawoot ◽  
David Saunders ◽  
Maneerat Rasameesoraj ◽  
Victor Melendez ◽  
Rawiwan Imerbsin ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Oral Bioavailability ◽  
Rhesus Monkeys ◽  
Antimalarial Activity ◽  
Ex Vivo ◽  
Absolute Bioavailability ◽  
Radical Cure ◽  
Concentration Time ◽  
Significant Difference

ABSTRACTThe pharmacokinetics, oral bioavailability, andex vivoantimalarial activity of mirincamycin isomers in a healthy rhesus monkey model were assessed to support lead optimization of novel nonhemolytic drugs for radical cure and causal prophylaxis of malaria. Fourteen male rhesus monkeys were randomized to four groups, which includedcisandtransisomers by the oral and intravenous routes, with vehicle-only controls for each dosing route. Concentration-time data were collected for 7 days and were analyzed by noncompartmental analysis.cis-Mirincamycin had an absolute oral bioavailability of 13.6%, which was slightly higher than that oftrans-mirincamycin (11.7%), but this difference was not statistically significant. There was a statistically significant difference between the area under the concentration-time curve from zero to 48 h (AUC0–48) ofcis-mirincamycin and that oftrans-mirincamycin after oral dosing. When culturedin vitrowith the W2 clone ofPlasmodium falciparum, the 50% inhibitory concentrations forcis-mirincamycin,trans-mirincamycin, and dihydroartemisinin were 11,300, 12,300, and 2.30 nM, respectively. However, when dosed primate plasma was culturedex vivoagainst the W2 clone, both isomers had much greater relative potencies than theirin vitroactivities relative to results for dihydroartemisinin, an increase of approximately 100-fold for thecisisomer and 150-fold for thetransisomer. Further, oralex vivoactivity was significantly higher than intravenous activity for both isomers, particularly during the first 90 min following dosing, suggesting the first-pass formation of one or more metabolites with blood-stage antimalarial activity. Identification of the metabolic pathways and metabolites may help to further delineate the properties of this class of drugs with previously demonstrated liver-stage antimalarial activity.

scholarly journals Lack of effect of vancomycin and gentamicin on auditory function in guinea pigs.

1996 ◽  
Vol 40 (5) ◽  
pp. 1098-1103
Author(s):  
K Nishihara ◽  
T Shimizu ◽  
H Kotaki ◽  
Y Sawada ◽  
T Okuno ◽  
...  
Keyword(s):  
Guinea Pigs ◽  
Hearing Threshold ◽  
Plasma Drug Concentration ◽  
Pharmacokinetic Parameters ◽  
Plasma Drug ◽  
Auditory Function ◽  
Time Data ◽  
Concentration Time ◽  
Penetration Ratio ◽  
Combined Administration

The dispositions of vancomycin (VCM) and gentamicin (GM) in plasma and perilymph after single and multiple administrations and the effects of multiple administrations of VCM or GM alone and the combination of both drugs on auditory function were studied in male guinea pigs. The pharmacokinetic parameters of VCM and GM obtained from plasma drug concentration-time data after single and multiple (22 days) intramuscular administrations of VCM (200 mg/kg of body weight) alone and GM (50 mg/kg) alone were not significantly different from those after combined administration of VCM (200 mg/kg) and GM (50 mg/kg). There was no change in the penetration ratio of VCM and GM into perilymph between administration of VCM or GM alone and the combination of both drugs. Furthermore, the hearing threshold of guinea pigs was not affected by VCM or GM alone or the combination of both drugs within the range of therapeutic VCM and GM levels in plasma in humans.

scholarly journals Preparation and Pharmacokinetic Study of Daidzein Long-Circulating Liposomes

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Qiao Wang ◽  
Wenjin Liu ◽  
Junjun Wang ◽  
Hong Liu ◽  
Yong Chen
Keyword(s):  
Single Dose ◽  
Drug Concentration ◽  
Drug Loading ◽  
Plasma Drug Concentration ◽  
The Body ◽  
Molar Ratio ◽  
Terminal Phase ◽  
Plasma Drug ◽  
Ultrasonic Time ◽  
Time Required

Abstract In this study, daidzein long-circulating liposomes (DLCL) were prepared using the ultrasonication and lipid film-hydration method. The optimized preparation conditions by the orthogonal design was as follows: 55 to 40 for the molar ratio of soybean phosphatidylcholine (SPC) to cholesterol, 1 to 10 for the mass ratio of daidzein to total lipid (SPC and cholesterol) (w:w), the indicated concentration of 5% DSPE-mPEG2000 (w:w), 50 °C for the hydration temperature, and 24 min for the ultrasonic time. Under these conditions, the encapsulation efficiency and drug loading of DLCL were 85.3 ± 3.6% and 8.2 ± 1.4%, respectively. The complete release times of DLCL in the medium of pH 1.2 and pH 6.9 increased by four- and twofold of that of free drugs, respectively. After rats were orally administered, a single dose of daidzein (30 mg/kg) and DLCL (containing equal dose of daidzein), respectively, and the MRT0−t (mean residence time, which is the time required for the elimination of 63.2% of drug in the body), t1/2 (the elimination half-life, which is the time required to halve the plasma drug concentration of the terminal phase), and AUC0−t (the area under the plasma drug concentration-time curve, which represents the total absorption after a single dose and reflects the drug absorption degree) of daidzein in DLCL group, increased by 1.6-, 1.8- and 2.5-fold as compared with those in the free group daidzein. Our results indicated that DLCL could not only reduce the first-pass effect of daidzein to promote its oral absorption, but also prolong its mean resident time to achieve the slow-release effect.

scholarly journals Oral Bioavailability and Pharmacokinetics of Trovafloxacin in Patients with AIDS

1999 ◽  
Vol 43 (12) ◽  
pp. 3005-3007 ◽  
Author(s):  
Melinda K. Lacy ◽  
David P. Nicolau ◽  
Charles H. Nightingale ◽  
Amy Geffken ◽  
Renli Teng ◽  
...  
Keyword(s):  
Oral Bioavailability ◽  
Active Form ◽  
Healthy Adults ◽  
Absolute Bioavailability ◽  
Randomized Design ◽  
The Mean

ABSTRACT Trovafloxacin pharmacokinetics were evaluated in 12 subjects with AIDS. By using a randomized design, single 200-mg doses of oral trovafloxacin and intravenous alatrofloxacin were administered. The mean absolute bioavailability was 91%. The pharmacokinetics of trovafloxacin when administered orally as the active form or intravenously as the prodrug (alatrofloxacin) are not altered in subjects with AIDS compared to those in healthy adults.

scholarly journals Investigations of ternary complexes of Co(II) and Ni(II) with thiodiacetate anion and 1,10-phenanthroline or 2,2’-bipyridine in aqueous solutions

2014 ◽  
Vol 13 (1) ◽  
Author(s):  
Dariusz Wyrzykowski ◽  
Joanna Pranczk ◽  
Dagmara Jacewicz ◽  
Aleksandra Tesmar ◽  
Bogusław Pilarski ◽  
...  
Keyword(s):  
Aqueous Solutions ◽  
Substitution Reactions ◽  
Experimental Conditions ◽  
Kinetic Measurements ◽  
Hydroxo Complexes ◽  
Binary Complexes ◽  
Vis Spectroscopy ◽  
Potentiometric Titration Method ◽  
The Stability ◽  
Ph Range

AbstractA potentiometric titration method (PT) and a stopped-flow kinetic technique monitored by a UV−Vis spectroscopy have been used to characterize the stability of series of Co(II)- and Ni(II)-thiodiacetato complexes, M(TDA), in the presence of 1,10-phenanthroline (phen) or 2,2’-bipyridine (bipy) in aqueous solutions. The stability constants of the binary (1:1), ternary (1:1:1) as well as the resulting hydroxo complexes were evaluated and compared to the corresponding oxydiacetate complexes. Based on the species distribution as a function of pH the relative predominance of the species in the system over a pH range was discussed. Furthermore, the kinetic measurements of the substitution reactions of the aqua ligands to phen or bipy in the coordination sphere of the binary complexes M(TDA) were performed in the 288–303 K temperature range, at a constant concentration of phen or bipy and at seven different concentrations of the binary complexes (0.2–0.5 mM). The kinetic stability of the M(TDA) complexes was discussed in relation to the experimental conditions and the kind of the auxiliary ligands (phen/bipy). Moreover, the influence of the type of primary ligand (thiodiacetate/oxydiacetate) on the substitution rate of the auxiliary ligands was also compared.

scholarly journals UV-VIS spectroscopy for monitoring yogurt stability during storage time

2016 ◽  
Vol 8 (30) ◽  
pp. 5962-5969 ◽  
Author(s):  
B. Aliakbarian ◽  
L. Bagnasco ◽  
P. Perego ◽  
R. Leardi ◽  
M. Casale
Keyword(s):  
Storage Time ◽  
Dairy Product ◽  
Entire Period ◽  
Vis Spectroscopy ◽  
The Stability ◽  
Color Texture

Color, texture and taste are key elements of a consumer's buying decision; thus, monitoring the stability of these features throughout the entire period of yogurt validity is fundamental for dairy product producers.

scholarly journals Buffer Additives and Packaging Differentially Influence the Stability of Dyes Commonly Used in Chromovitrectomy

2016 ◽  
Vol 1 (3) ◽  
pp. 1-10
Author(s):  
Begoña Parrado Aliod ◽  
Wilfried Kugler ◽  
Tim Häring
Keyword(s):  
Polyethylene Glycol ◽  
Chemical Stability ◽  
Deuterium Oxide ◽  
Oxidative Degradation ◽  
Bromophenol Blue ◽  
Physiological Range ◽  
Vis Spectroscopy ◽  
The Stability ◽  
Acid Violet ◽  
Dye Solutions

Purpose: This study was performed to investigate the chemical stability of different dyes used in chromovitrectomy and the influence of various product parameters on it. Methods: Buffered dye solutions were prepared containing 1.5 g/L acid violet 17, 0.25 g/L brilliant blue G, 1.3 g/L bromophenol blue, and 1.5 g/L trypan blue, combined with deuterium oxide, polyethylene glycol 3350, and D-mannitol as additives. For accelerated storage testing, samples were incubated for 400 h at 80°C corresponding to 2 years according to the Van ‘t Hoff equation. After different incubation times samples were taken for UV/Vis spectroscopy, pH measurement, and osmometry. Results: Depending on dye, additive, and packaging, different solutions exhibit differences in chemical stability and hence shelf life. Packaging in syringes instead of vials increases dye stability. Additives may negatively influence important parameters, e.g. polyethylene glycol 3350 increases osmolality beyond the physiological range. Notably, acid violet 17 is chemically unstable except in D-mannitol-containing buffer, packed in syringes. However, simultaneously, D-mannitol leads to a pH shift below 7.0. Conclusion: In summary, dye solutions filled in syringes should be preferred to vials to slow down oxidative degradation. Especially acid violet 17 solutions should be used with caution because the addition of D-mannitol may contribute to pH values beyond the physiological range.

Sign in / Sign up

Export Citation Format

Share Document