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Biomedical subjects

R Panchagnula

Publications and source records attributed to R Panchagnula.

At least 37 records · Page 2Linked to original sources
PubMed2001

Drug delivery: an odyssey of 100 years.

Drug delivery has metamorphosed from the concept of a pill to molecular medicine in the past 100 years. Better appreciation and integration of pharmacokinetic and pharmacodynamic principles in design of drug delivery systems has led to improved therapeutic efficacy. A greater understanding of the molecular transport in relation to physico-chemical properties has led to the evolution of a biopharmaceutics classification system, which should be a future road map, governing drug design, development and delivery. While drugs belonging to class I and II will be delivered by established platform technologies, novel delivery strategies will evolve and mature to realize the potential of 'new generation' biotech and non biotech drugs belonging to class III and IV, respectively.

Drug Delivery Systems↗
PubMed2001

Polymers in drug delivery.

Advances in polymer science have led to the development of several novel drug-delivery systems. A proper consideration of surface and bulk properties can aid in the designing of polymers for various drug-delivery applications. Biodegradable polymers find widespread use in drug delivery as they can be degraded to non-toxic monomers inside the body. Novel supramolecular structures based on polyethylene oxide copolymers and dendrimers are being intensively researched for delivery of genes and macromolecules. Hydrogels that can respond to a variety of physical, chemical and biological stimuli hold enormous potential for design of closed-loop drug-delivery systems. Design and synthesis of novel combinations of polymers will expand the scope of new drug-delivery systems in the future.

Biodegradation, Environmental↗
PubMed2001

Antituberculosis drugs and new drug development.

Tuberculosis affects more than 8 million people and has serious repercussions on economic, psychologic, and social status. Since its declaration as a global emergency in 1993 by the World Health Organization, significant development in the treatment and control of tuberculosis has been the implementation of the short-course directly observed treatment along with fixed dose combinations of existing drugs. However, the currently available therapeutic regimens have inherent disadvantages of long treatment duration, patient noncompliance, and risk of drug resistance. Hence, new antituberculosis drugs that are potent, are active against resistant strains and latent forms, and reduce the treatment period are needed to combat this disease. In this review, the authors discuss new chemical entities that in their opinion have a potential to become new antituberculosis drugs. This article emphasizes the role of biopharmaceutics and pharmacokinetics as an indispensable part in the development of new antituberculosis drugs to overcome the common hurdles such as exorbitant cost, time, and attrition rate involved in the process.

Animals↗
PubMed2001

Pharmacokinetic study of paclitaxel as a 3-hour infusion in an Indian population: 135 mg/m2 vs. 175 mg/m2.

The objective of this clinical study was to determine the pharmacokinetic parameters of paclitaxel at doses of 135 and 175 mg/m2 when given as a 3-hour infusion in an Indian population. Twelve cancer patients of both sexes participated in the study and a parallel experimental design was adopted for the assignment of doses to patients. A solid phase extraction technique was used for sample clean-up followed by a reversed phase HPLC assay for the analysis of paclitaxel in plasma samples. Pharmacokinetic parameters such as Cmax, AUC0-infinity, T1/2 beta, AUMC0-infinity, VSS, VZ and CLT were determined by a compartment model-independent method using a PCNONLIN package. Teff and AUCeff were also calculated and compared at the two doses by considering a plasma concentration of > or = 0.05 microM as threshold. The mean Cmax and AUC0-infinity values were 2.57 microM and 12.06 microM at the 135 mg/m2 dose level while at the 175 mg/m2 dose the values increased to 4.96 microM and 9.52 microM.h/l, respectively. It was found that the 135 mg/m2 dose resulted in greater mean CLT and VSS values than the 175 mg/m2 dose. The disposition of paclitaxel was found to be nonlinear and the pertinent pharmacokinetic parameters were comparable to those from previous clinical studies. It was concluded from the present study that further clinical trials of paclitaxel alone or in combination with other drugs should be undertaken cautiously, taking into consideration its nonlinear pharmacokinetics which necessitate proper adjustment of the infusion schedule and/or dose to avoid any adverse consequences to the patient.

Adult↗
PubMed2001

Bioequivalence of isoniazid in a two drug fixed dose combination and in a single drug dosage form.

To increase the patient compliance and reduce the risk of drug resistant strains, WHO and IUATLD recommend the use of Fixed Dose Combination (FDC) tablets as a routine therapeutic regimen in Directly Observed Treatment Shortcourse (DOTS). But the main issue in the use of FDC is the quality of the formulation. At present WHO and IUATLD suggest the bioequivalence assessment of only rifampicin from FDC compared to separate formulations. For the therapeutic effectiveness all the components of the FDCs should be bioavailable at tissue site. Also, the primary and acquired resistance rate of isoniazid is much higher compared to other anti-tubercular drugs. Hence, a comparative bioavailability study of isoniazid from a two drugs FDC compared to a separate formulation was carried out on a group of 12 healthy volunteers. When evaluated by normal or log transformed confidence interval, Two Way ANOVA and Hauschke analysis, the bioequivalence limits for AUC0-8 and AUC0-24 were within 0.8-1.25. For Cmax and Tmax, these limits were within 0.7-1.43. Hence, isoniazid from a FDC formulation was found to be bioequivalent to a separate formulation at same dose levels.

Adolescent↗
PubMed2000

Skeletal drug delivery systems.

Selective drug delivery to any organ becomes very important in certain diseases and clinical manifestations, especially when the drug affects other exposed tissues adversely. The importance of selective drug action is still further increased when the affected part is poorly perfused. Although a network of blood vessels is present throughout skeletal tissue (or bone), it is not sufficient for immediate delivery of drugs to the desired site of action in the tissue and in sufficient amounts over appropriate time periods. Hence, selective drug delivery to the skeletal system has remained a great challenge to pharmaceutical scientists over the years. However, in the recent past, attention has been focused on the importance of skeletal drug delivery and the first Skeletal Drug Delivery System (SDDS) was introduced by Bucholz and Engelbrecht in 1970 for the delivery of drugs to skeletal tissues at a high concentration to achieve desirable therapeutic effects. SDDS is used to deliver the drug directly to skeletal tissue through self-setting cement, which also acts as a bone filler, thereby improving the therapeutic effectiveness of drugs in bone diseases. The present review highlights the applicability of various materials as bone fillers for the purpose of skeletal drug delivery.

Animals↗
PubMed2000

Biopharmaceutics and pharmacokinetics in drug research.

With the synergistic and multiplicative interactions of rational drug design, recombinant biotechnology, combinatorial chemistry and high-throughput screening, millions of compounds are being synthesized by chemists. However, development of these drug candidates has often been impeded, if not terminated, due to biopharmaceutic and/or pharmacokinetic constraints. This has resulted in delays in development time and escalation of cost in the drug research programmes. So, the present emphasis is to reduce development time and cost, which is analogous to added patent life besides the enormous reduction in human suffering. In this compilation the important biopharmaceutic and pharmacokinetic approaches are discussed, which will help in the development of safe and more efficacious drugs with reduced development time and cost.

Biopharmaceutics↗
PubMed2000

Transdermal iontophoresis revisited.

Iontophoresis evolved as a transdermal enhancement technique in the 20th century, primarily for the delivery of large and charged molecules. Significant achievements have been made in the understanding of underlying mechanisms of iontophoresis and these have contributed to the rational development of iontophoretic delivery systems. The major challenges in this area are the development of portable, cost effective devices and suitable semi-solid formulations that are compatible with the device and the skin. Some of the obstacles in transdermal iontophoresis can be overcome by combining iontophoresis with other physical and chemical enhancement techniques for the delivery of macromolecules. Iontophoresis also offers an avenue for extracting information from the body through the use of reverse iontophoresis, which has potential application in diagnosis and monitoring. The current research is focussed towards resolving the skin toxicity issues and other problems in order to make this technology a commercial reality.

Administration, Cutaneous↗
PubMed2000

Nicotine transdermal systems: pharmaceutical and clinical aspects.

Smoking is creating a burden on the healthcare budgets all over the world. Management of nicotine dependence is difficult due to the so-called pleasurable effects experienced by smokers. Among the various treatment approaches, nicotine replacement therapy, where nicotine from cigarettes is replaced with nicotine from a relatively safer delivery vehicle, has been successful. Transdermal delivery of nicotine is an effective type of nicotine replacement therapy due to inherent pharmacokinetic advantages over other routes of delivery. Several nicotine transdermal delivery systems are available to suit the varying needs of smokers and have been found to be clinically patient friendly and well tolerated. This review focuses on the various clinical and pharmaceutical aspects of nicotine with special emphasis on transdermal delivery systems.

Administration, Cutaneous↗
PubMed2000

Bioequivalence of rifampicin when administered as a fixed-dose combined formulation of four drugs versus separate formulations.

A bioequivalence study of the antitubercular drug rifampicin in a four-drug combination (rifampicin, isoniazid, pyrazinamide and ethambutol) and separate formulations of the drugs at the same dose levels was carried out in a group of 22 healthy male volunteers. The investigation was designed as an open crossover study. The drugs were administered once in individual formulations and once in a fixed-dose combination. The WHO-approved protocol was followed according to which six blood samples were collected over a period of 8 h for each volunteer and each experimental session. Pooled urine samples were also collected during the study. Rifampicin and desacetyl rifampicin concentrations in both plasma and urine samples were assessed. Various pharmacokinetic parameters such as AUC0-8 h, Cmax and Tmax were calculated for both rifampicin and desacetyl rifampicin. The results indicated that combined (the four-drug combination) and separate formulations are bioequivalent for rifampicin.

Adult↗
PubMed2000

Evaluation of rifampicin bioequivalence in fixed-dose combinations using the WHO/IUATLD recommended protocol.

For an accurate assessment of rifampicin bioequivalence from fixed-dose combinations (FDCs), and to reduce the time and cost constraints associated with bioequivalence studies, the World Health Organization and the International Union Against Tuberculosis and Lung Disease have developed a simplified screening protocol. This study was undertaken with the objective of testing the applicability of this protocol for all types of FDCs. Data were obtained for volunteers common to three studies, and pharmacokinetic parameters were evaluated by different statistical tests. From the results, it has been demonstrated that the simplified screening protocol is suitable for evaluating the bioequivalence of rifampicin in all the types of FDCs available on the market.

Adult↗
PubMed2000

Non familial juvenile polyposis presenting as chronic intestinal obstruction.

Juvenile polyps are the commonest colonic polyps seen in children and present most often with rectal bleed. Intussusception is an extremely rare presentation in juvenile polyposis (JP) syndrome. This case highlights the rare association of ileo-colic intussusception with non-familial Juvenile Polyposis.

Biopsy, Needle↗
PubMed2000

Wolman's disease--a case report.

Wolman's disease is a rare autosomal recessive lysosomal storage disorder. We report a case, which we identified with foamy histiocytes in bone marrow and adrenal calcification in radiological imaging. The diagnosis can be made on minimal investigation when clinically suspected. But cytogenetic study is required to substantiate the diagnosis further.

Adrenal Gland Diseases↗
PubMed1999

Localized paclitaxel delivery.

While the search for new antineoplastic agents is in progress, optimization of delivery for existing drugs will remarkably improve the current scenario in the management of cancer. Paclitaxel, a new antineoplastic agent, is one such drug deserving attention in the field of regional drug delivery, offering immense pharmacokinetic as well as therapeutic advantage via localized delivery. The antiangiogenic activity of paclitaxel has been demonstrated using the chick chorioallantoic membrane model (CAM). This review focuses on the antiangiogenic activity of paclitaxel supported by the evidence that angiogenesis inhibitors display potential synergism with cytotoxic agents in the treatment of primary and metastatic cancers. Preclinical trials have confirmed that the biological and cytotoxic effects of paclitaxel on several tumor cell lines are enhanced by the increase in both the drug concentration and the duration of exposure. Sufficient experimental evidence has accumulated to state that localized delivery will exploit the multiple pharmacological effects of paclitaxel in the treatment of refractory and metastatic cancerous diseases. The drug delivery systems, namely, microspheres, surgical pastes and implants, fabricated for localized paclitaxel delivery are reviewed explaining the concept of increased tumor burden alleviating body burden as a consequence of such delivery systems. Some of the preclinical trials are very encouraging and speculate a promising future for these devices in the battle against solid tumors. Finally, the review briefs on the possibilities for better paclitaxel delivery and the future drug delivery systems for localized cancer chemotherapy.

Animals↗