Preclinical Pharmacokinetic Evaluation of Efavirenz Solid Dispersions in Two New Modified Starches

Chowdary, K. P. R.; Enturi, Veeraiah
April 2013
Journal of Applied Pharmaceutical Science;SUP2013, Vol. 3, pS89
Academic Journal
Efavirenz, a widely prescribed anti retroviral drug belong to Class II under BCS and exhibit low and variable oral bioavailability due to its poor aqueous solubility and it requires enhancement in solubility and dissolution rate for increasing its oral bioavailability. In our earlier studies solid dispersion of efavirenz in two new modified starches namely (i) starch citrate and (ii) starch phosphate has markedly enhanced the dissolution rate and dissolution efficiency of efavirenz. The objective of the present study is to evaluate the in vivo performance and pharmacokinetics of the efavirenz solid dispersions in the two new modified starches. Pharmacokinetic evaluation of efavirenz- starch citrate (1:2) and efavirenz- starch phosphate (1:2) solid dispersions was done in healthy rabbits weighing 1.5 - 2.5 kg (n=6) of either sex in a cross over RBD at a dose equivalent to 10 mg/kg of drug in comparison to efavirenz pure drug. All the pharmacokinetic parameters namely Cmax, Tmax, Ka and (AUC)∞0 indicated rapid and higher absorption and bioavailability of efavirenz when administered as solid dispersion in the two new modified starches. A 9.90 and 9.14 fold increase in the absorption rate (Ka) was observed respectively with efavirenz- starch citrate (1:2) solid dispersion and efavirenz- starch phosphate (1:2) solid dispersion when compared to efavirenz pure drug. A 1.46 and 1.47 fold increase in (AUC)∞0 was also observed respectively with these solid dispersions when compared to efavirenz pure drug. The solid dispersions of efavirenz in the two new modified starches (starch citrate and starch phosphate) exhibited markedly higher rates of absorption and bioavailability of efavirenz when compared to efavirenz alone in the in vivo evaluation.


Related Articles

  • HIV/AIDS Patients Display Lower Relative Bioavailability of Efavirenz than Healthy Subjects. Mukonzo, Jackson K.; Nanzigu, Sarah; Rekig, Dinko; Waako, Paul; Röshammar, Daniel; Ashton, Michael; Ogwal-Okeng, Jasper; Gustafsson, Lars L.; Aklillu, Eleni // Clinical Pharmacokinetics;2011, Vol. 50 Issue 8, p531 

    Background: Pharmacokinetic studies of antiretroviral drugs are often conducted in adult healthy subjects, and the results are extrapolated to HIV/AIDS patients. HIV/AIDS, however, is known to cause morphological and physiological changes that may alter the pharmacokinetics of antiretroviral...

  • Enhancement of Aqueous Solubility and Oral Bioavailability of Nelfinavir by Complexation with ß- Cyclodextrin. Kumari, Shilpi; Bhawar, Ganesh T.; Musmade, Prashant B.; Lewis, Shaila // Tropical Journal of Pharmaceutical Research;Aug2015, Vol. 14 Issue 8, p1333 

    Purpose: To determine if complexation with β- cyclodextrin (β-CD) increases water solubility and subsequent bioavailability of nelfinavir mesylate (NM). Methods: Complexation of NM with β-CD in 1:1.5 molar ratio was carried out by solvent evaporation, freeze-drying and kneading methods....

  • Solubilization of Hydrophobic Antitumor Drugs (Review). Gulyakin, I.; Oborotova, N.; Pechennikov, V. // Pharmaceutical Chemistry Journal;Jun2014, Vol. 48 Issue 3, p209 

    Advances in chemotherapy always depend on the physician's correct selection of a medicinal formulation in which the main active ingredient or complex of substances has the greatest therapeutic effect. From this point of view, the pharmacokinetics of injectable medicinal formulations are optimal...

  • Pharmacokinetics of platinum after oral or intravenous cisplatin: a phase 1 study in 32 adult patients. Urien, Saik; Brain, Etienne; Bugat, Roland; Pivot, Xavier; Lochon, Isabelle; Van, Marie-Louise; xe7;oise#Vauzelle, Fran&; xe7;ois#Lokiec, Fran& // Cancer Chemotherapy & Pharmacology;Jan2005, Vol. 55 Issue 1, p55 

    Aims: To develop a population pharmacokinetic model for simultaneous analysis of oral/intravenous cisplatin data in order to estimate the mean population pharmacokinetic parameters, mainly the bioavailability, of cisplatin and to evaluate the influence of covariates on the pharmacokinetic...

  • Intrinsic oxidative stress in cancer cells: a biochemical basis for therapeutic selectivity. Hileman, Elizabeth Oldham; Liu, Jinsong; Albitar, Maher; Keating, Michael J.; Huang, Peng // Cancer Chemotherapy & Pharmacology;Mar2004, Vol. 53 Issue 3, p209 

    Purpose. Therapeutic selectivity is one of the most important considerations in cancer chemotherapy. The design of therapeutic strategies to preferentially kill malignant cells while minimizing harmful effects to normal cells depends on our understanding of the biological differences between...

  • Oral bioavailability of docetaxel in combination with OC144-093 (ONT-093). Kuppens, I.; Bosch, T.; Maanen, M.; Rosing, H.; Fitzpatrick, A.; Beijnen, J.; Schellens, J. // Cancer Chemotherapy & Pharmacology;Jan2005, Vol. 55 Issue 1, p72 

    Objective: Docetaxel given orally as monotherapy results in low bioavailability of < 10%. Previous studies have indicated that the intestinal efflux pump P-glycoprotein (P-gp) prevents uptake from the gut resulting in low systemic exposure to docetaxel. The purpose of this study was to determine...

  • Approaches to Improve the Oral Bioavailability and Effects of Novel Anticancer Drugs Berberine and Betulinic Acid. Godugu, Chandraiah; Patel, Apurva R.; Doddapaneni, Ravi; Somagoni, Jaganmohan; Singh, Mandip // PLoS ONE;Mar2014, Vol. 9 Issue 3, p1 

    Background: The poor bioavailability of Berberine (BBR) and Betulinic acid (BA) limits the development of these promising anticancer agents for clinical use. In the current study, BBR and BA in spray dried (SD) mucoadhesive microparticle formulations were prepared. Methods: A patented dual...

  • PRECLINICAL PHARMACOKINETIC EVALUATION OF EFAVIRENZ - CYCLODEXTRIN - PVP INCLUSION COMPLEXES. Chowdary, K. P. R.; Devi, G. S. Annamma // International Journal of Pharmaceutical Sciences Review & Resear;Jul/Aug2012, Vol. 15 Issue 1, p23 

    Efavirenz, a widely prescribed anti retroviral drug belongs to class II under BCS and exhibit low and variable oral bioavailability due to its poor aqueous solubility. Its oral absorption is dissolution rate limited and it requires enhancement in the solubility and dissolution rate for...

  • Prehepatic metabolism of drugs - a mechanism for low and variable oral bioavailability. Hoppu, Kalle // Pediatric Nephrology;1999, Vol. 13 Issue 1, p85 

    Summarizes various research on oral drug bioavailability, compiled as of January 1999. Identification of glucocorticoid-inducible cytochromes P-450 in the intestinal mucosa of rats and man; Identification of rifampicin-inducible P450III4 in human small bowel electrocytes; Bioavailability of...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics