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Biomedical subjects

D R Krishna

Publications and source records attributed to D R Krishna.

At least 37 records · Page 2Linked to original sources
PubMed1993

In vitro and in vivo studies on slow release propranolol hydrochloride suppositories. Pharmacokinetic and pharmacodynamic evaluation.

Matrix-based slow release (SR) compressed propranolol HCl (25 mg) suppositories were formulated using PEG 4000 and either stearic acid or bees wax at different concentrations (5, 7.5 and 10%). In vitro studies revealed good slow release characteristics from the suppositories. Their in vivo performances--pharmacokinetics and pharmacodynamics--were evaluated in rabbits. Different pharmacokinetic parameters were determined from the plasma concentration-time profiles using a model-independent computer programme, RAMKIN. The relative bioavailability of propranolol (CAS 525-66-6) from three SR suppositories containing stearic acid, 7.5 and 10% and bees wax, 5%, was 86.4, 87.8, and 83.6% respectively. Pharmacodynamic response (beta-blockade) was assessed by determining the degree of reduction of isoprenaline-induced tachycardia at different time intervals. A minimum concentration of 40-60 ng/ml drug in plasma was maintained during 1-10 h, and there has been a minimum of about 40-50% of beta-blockade during 1-9 h post administration. A good correlation between pharmacokinetic and pharmacodynamic profiles was observed.

Animals↗
PubMed1992

High-performance liquid chromatographic determination of usnic acid in plasma.

A high-performance liquid chromatographic method for the determination of usnic acid in human plasma using diclofenac sodium as internal standard is described. Plasma proteins were precipitated with methanol. A 250 mm x 4 mm I.D. Nucleosil. C18 (5 microns) column with a mobile phase consisting of methanol-phosphate buffer (pH 7.4) (70:30, v/v) was used. Chromatography was performed at ambient temperature with flow-rate of 1 ml min-1 and ultraviolet detection at 280 nm. Each analysis required no longer than 7 min. Quantification was achieved by measurement of the peak-height ratio and the absolute recovery varied from 93.8 to 97.3%. The limit of quantitation of usnic acid in plasma was 0.25 micrograms ml-1. The intra-day relative standard deviation (R.S.D.) ranged from 1.24 to 4.53% and the inter-day R.S.D. from 2.23 to 8.25% at three different concentrations. The method was applied to the determination of plasma levels of usnic acid after intravenous and oral administration to study its disposition in a healthy male rabbit.

Administration, Oral↗
PubMed1991

Mitodepressive, clastogenic and biochemical effects of (+)-usnic acid in mice.

Mice were treated orally with aqueous suspensions of (+)-usnic acid in a single dose of either 100 or 200 mg/kg. The effects on femur cells and proteins and on nucleic acids of liver cells were studied 24-72 h after treatment. (+)-Usnic acid was found to affect the proliferation of polychromatic erythrocytes possibly by interference with RNA biosynthesis. The slight increase in the micronucleated polychromatic erythrocytes without affecting DNA synthesis suggests an effect of usnic acid on spindle apparatus.

Administration, Oral↗
PubMed1990

Famotidine. Pharmacokinetic properties and suppression of acid secretion in paediatric patients following cardiac surgery.

The pharmacokinetic and pharmacodynamic properties of the H2-receptor antagonist famotidine have been well described in adult subjects. However, similar data for children are not available. Therefore, this study looked at the disposition of the drug (given to prevent aspiration following cardiac surgery) in 10 paediatric patients with normal kidney function (age range 2 to 7 years, bodyweight 14 to 25 kg) after a single intravenous dose of famotidine 0.3 mg/kg. Plasma concentrations of the drug and gastric pH values were both monitored for 20 hours by high performance liquid chromatography and aspiration of gastric juice, respectively. Plasma famotidine concentrations declined with an elimination half-life of 3.3 +/- 1.8 h (mean +/- SD) and the drug was effective in elevating the gastric pH above 3.5 for about 9 hours in 6 patients. The variable volume of distribution and total plasma clearance of famotidine averaged 1.4 +/- 1.0 L/kg and 0.3 +/- 0.17 L/h/kg, respectively. In 4 patients unchanged famotidine could also be measured in a 12-hour urine fraction. The amount excreted (21 to 79%) correlated with clearance (r = 0.97). All these data are comparable to those obtained in healthy adults, indicating that paediatric patients receiving intensive medical treatment after cardiac surgery can handle famotidine in a way very similar to healthy adult subjects. A dosage of 0.3 mg/kg every 8 hours appears to be advisable.

Cardiac Surgical Procedures↗
PubMed1989

Detection of desmethyldiazepam and diazepam in brain of different species and plants.

Recent data suggest that desmethyldiazepam (DD), a major metabolite of several benzodiazepines (BZD), might be of natural origin. Therefore we tried to quantify DD and diazepam (D) in animals during maturation (e.g. hen, chicken, eggs), in brain of species at different evolutionary stages e.g. salmon, frog, monitor/reptile, rat, cat, dog, deer, bovine) including newborn and adult humans. Since low concentrations of DD (range 0.01-0.04 ng/g wet wt) and D (range 0.005-0.02 ng/g) could be measured in different species by sensitive and specific mass spectrometry (GC-MS), we analysed also several plants (e.g. maize corn, lentils, potatoes, soybeans, rice, mushrooms). Again, DD and D could be detected in low amounts (0.005-0.05 ng/g) in some plant products. This would suggest that DD and D might be of natural origin and incorporated via the foodchain into the animal and human body. The biological role or clinical relevance of these intriguing findings need still to be elucidated.

Animals↗
PubMed1989

Frequent non-response to histamine H2-receptor antagonists in cirrhotics.

The effect of ranitidine 300 mg po given at 1800 h (famotidine 40 mg/cimetidine 800 mg) on the night time gastric pH was tested using longterm intragastric pH monitoring in 27 patients with and 32 patients without liver cirrhosis. A rise in the gastric pH above 4.0 for more than six hours between 1800 h and 0600 h was considered as sufficient effect (response) of the H2-receptor antagonists on gastric acidity. Among the patients with cirrhosis, there were significantly (p less than 0.005) more non-responders to ranitidine (16 of 27 patients) than in the control group (six of 32). When 13 of the 22 non-responders to ranitidine were subsequently treated with famotidine, only two showed a sufficient rise in their gastric pH. Of the 11 patients not responding to both H2-receptor antagonists, 10 were finally treated with cimetidine and eight did not respond. Plasma levels of all three drugs measured two and four hours after oral administration were not significantly different between cirrhotic and noncirrhotic patients as well as between responders and non-responders. In addition, in all patients plasma levels were far above the corresponding IC50 values. Therefore, differences in the absorption and plasma levels of these drugs cannot account for the frequent non-response in cirrhotics.

Anti-Ulcer Agents↗
PubMed1989

New approach to curb the transmission of leprosy.

The effect of local treatment of nose of lepromatous type of patients with different formulations of rifampicin nasal drops/sprays was investigated in a large number of patients. The preparations were either sprayed or instilled into the nostrils after flushing the nostrils with normal saline at 37 degrees C. It was observed that 10 mg/ml of rifampicin was effective in reducing the BI and MI to zero in nose in seven days in majority of the patients. No untoward effect was seen in any of the patients. It is suggested that nasal sprays/drops may be able to prevent the transmission of hanseniasis, as nose is recognised to be an important portal of exit of M. leprae. Further when rifampicin drops/sprays are used as soon as the diagnosis is made, the nasal deformity may be prevented. It is believed that local treatment along with systemic therapy would go a long way in controlling the transmission of hanseniasis.

Administration, Intranasal↗
PubMed1988

Pharmacokinetics of ranitidine in patients undergoing haemofiltration.

The pharmacokinetics of ranitidine was investigated in 11 patients with acute or end stage renal failure during haemofiltration. Each patient received 50 mg ranitidine i.v. The mean distribution and elimination half lives were 0.13 and 2.57 h, respectively. The total body clearance (CL) and volume of distribution (Vz) were 298 ml.min-1 (5.19 ml.min-1.kg-1) and 1.08 l.kg-1, respectively. About 17.1% of the administered dose was removed by haemofiltration (in approximately 20 l filtrate). Five of the patients still had some urine output and they excreted 0.1 to 11.8% of the dose in urine in 24 h. The haemofiltration clearance was 66.9 ml.min-1 at a filtrate flow rate of 86 ml.min-1, corresponding to a mean sieving coefficient of 0.78 (n = 6). As plasma concentrations were still in an effective range after haemofiltration, dose supplementation is not recommended.

Acute Kidney Injury↗
PubMed1988

Pharmacokinetics and dynamics of famotidine in patients with renal failure.

1. Famotidine, a new histamine H2-receptor antagonist was administered intravenously (20 mg) to 22 patients with end stage renal disease during a dialysis free interval (n = 6) and during different blood purification processes including haemodialysis (HD; n = 4), intermittent haemofiltration (HF; n = 4), continuous haemofiltration (CHF; n = 4) and continuous ambulatory peritoneal dialysis (CAPD; n = 4). The plasma, the dialysate/filtrate and the urine concentrations of famotidine were analysed by h.p.l.c. 2. In addition, intra-gastric pH was measured by a long-term-pH probe in seven patients with renal failure and in six patients with normal renal function (control group) following 20 mg famotidine. 3. A 7 to 10 fold prolongation of famotidine's elimination half-life (27.2 +/- 8.5 h; mean +/- s.d.) was observed in patients with renal failure as compared with the half-life (2.6-3.6 h) in subjects with normal renal function. 4. Total body clearance (CL) and volume of distribution (V) were found to be 33.5 +/- 10.1 ml min-1 and 1.3 +/- 0.7 l kg-1, respectively in patients with end-stage renal failure. 5. Blood purification processes have shown considerable variation in clearing famotidine from the body: 16.4 +/- 8.9 and 6.0 +/- 2.9% of the administered dose in HD with polysulphone and cuprophan membranes respectively, 7.7 +/- 5.2% in HF with a polyacrylonitrile membrane (each for 5 h), 4.5 +/- 1.1% in CAPD and 16.2 +/- 4.9% in CHF with a polysulphone membrane within 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Newer H2-receptor antagonists. Clinical pharmacokinetics and drug interaction potential.

Since H2-receptor antagonists are widely and successfully used in the treatment of peptic ulcer, several alternatives to the standard agents cimetidine and ranitidine have been developed. Promising 'new' candidates might be famotidine and nizatidine. For proper selection of the appropriate drug, its pharmacokinetic properties and interaction potential should be known. All 'old' and 'new' H2-receptor blockers are eliminated relatively rapidly (t 1/2 ranges from 1.5 to 4 hours), mainly by the renal route (glomerular filtration and tubular secretion). They exhibit a linear disposition and their distribution is similar. Absorption is most complete for nizatidine, whereas famotidine demonstrates the lowest effective plasma concentrations. Since etintidine shares the same imidazole ring structure as cimetidine, it can also impair oxidative drug metabolism in the liver. In this respect, the non-interacting famotidine and nizatidine (like ranitidine) offer a definite advantage. Based on their very similar pharmacokinetic and interaction profiles, these 2 H2-receptor antagonists might be regarded as alternatives to the older drugs in this group, and at least some economic benefits might result from the competition they will provide.

Drug Interactions↗
PubMed1983

How much non-infectious are the "non-infectious" lepromatous leprosy patients?

Nose forms an important site at which the M. leprae in lepromatous leprosy (LL) patients lodge and multiply. Nose forms an important reservoir for M. leprae, from where they may be transmitted to healthy contacts. Inspite of realizing the above fact, nose does not normally receive due importance during the chemotherapy of leprosy. LL patients, after regular treatment with dapsone or rifampin for about 20 wks and 3 wks respectively are normally considered non-infectious. From the present investigation it is clear that local treatment of the ones with a bactericidal agent should perhaps be necessary during chemotherapy of LL patients to make them non-infectious and to control the transmission of the disease.

Clofazimine↗
PubMedDate not supplied

Pharmacokinetics of d(+)-usnic acid in rabbits after intravenous administration.

The pharmacokinetics of usnic acid, a lichen antitubercular, antitumor and enzyme inhibiting agent, was studied in normal male rabbits after administration of 5 mg/kg dose by intravenous route. Plasma samples were collected up to 48 h. The plasma usnic acid levels showed a triexponential decay with a terminal half life of 10.69 h. The mean volume of distribution of the central compartment was 43.93 ml/kg. The pharmacokinetic parameters obtained from a three-compartment body model and a noncompartment body model gave close values. The mean steady-state volume of distribution was 167.17 and 163.29 ml/kg, systemic clearance was 12.17 and 12.25 ml/h/kg and AUC was 428.51 and 426.69 micrograms.ml/h following three-compartmental and noncompartmental analyses respectively.

Animals↗
PubMedDate not supplied

Pharmacokinetics of D(+)-usnic acid in rabbits after intravenous and oral administration.

The pharmacokinetics of D(+)-usnic acid--a lichen antitubercular, antitumor, and enzyme-inhibiting agent--was studied in rabbits following intravenous or oral administration of 5 and 20 mg/kg body weight doses, respectively. Plasma samples were collected at different time intervals, and usnic acid was determined by HPLC. Plasma usnic acid levels following intravenous administration showed a triexponential elimination with a mean +/- SD terminal half-life of 10.7 +/- 4.6 hr. The volume of distribution of the central compartment and systemic clearance were 43.9 +/- 21.3 ml/kg and 12.2 +/- 3.0 ml/hr/kg, respectively. Pharmacokinetic parameters obtained, based on compartmental and noncompartmental approaches, were comparable. Plasma concentration data obtained after oral administration were analyzed using a noncompartmental method. Peak plasma level (Cmax) of 32.5 +/- 6.8 micrograms/ml was achieved in 12.2 +/- 3.8 hr (tmax). Mean absolute bioavailability of usnic acid following oral administration was 77.8%.

Administration, Oral↗
PubMedDate not supplied

Oxidative stress and anti-oxidant status in leprosy patients.

Severe oxidative stress has been reported in leprosy patients because of malnutrition and poor immunity. The purpose of this study was to investigate the serum lipid peroxidation products, serum LDH and important free radical scavenging enzymes, i.e. superoxide dismutase (SOD), and catalase and anti-oxidant glutathione levels and total anti-oxidant status, in different types of leprosy patients. The subjects for this study were normal human volunteers (NHVs, n=14), paucibacillary leprosy patients (PB, n=18), untreated MB patients (MB1, n=18), MB patients under treatment (MB2, n=19), and MB patients released from treatment (RFT) (MB3, n=28). The levels of lipid peroxidation product, malondialdehyde (MDA), and LDH increased significantly (p<0.001) in MB (MB1, MB2, MB3) patients, and both gradually decreased with clinical improvement following MDT. The levels of SOD, catalase and glutathione, and the total anti-oxidant status decreased significantly in MB (MB1, MB2, MB3) patients (p<0.001), in comparison with NHVs. They gradually increased with clinical improvement with MDT. There was no significant variation of these parameters in PB leprosy patients in comparison with healthy volunteers. High free radical activity and low anti-oxidant levels observed in MB (MB1, MB2, MB3) leprosy patients indicate that there is an oxidative stress in MB cases, irrespective of the treatment status and suggest a suitable anti-oxidant therapy to prevent possible tissue injury.

Antioxidants↗
PubMedDate not supplied

Disposition of rifampicin following intranasal and oral administration.

Leprosy is transmitted by dissemination of M.leprae which are lodged in the nose of the patients suffering from multibacillary (MB) type of the disease. Rifampicin, a potent bactericidal antileprotic drug is given orally to the patients with a view to make the infective cases non-infective. Earlier work by us has shown that intranasal administration of rifampicin helps in reducing the M.leprae load in the nose much faster than after conventional oral administration. In the present study, rifampicin concentrations in plasma/urine/nasal wash of healthy volunteers following oral and intranasal administration were determined. Following intranasal administration, rifampicin was not detectable in plasma and high concentrations were measured in the nasal wash. Following oral administration, rifampicin was not detectable in the nasal wash indicating that enough antibiotic levels are not available for clearing M.leprae from nose.

Administration, Intranasal↗