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Biomedical subjects

J S Kaka

Publications and source records attributed to J S Kaka.

16 recordsLinked to original sources
PubMed1992

Bioavailability of ibuprofen from oral and suppository preparations in rats.

Bioavailability of ibuprofen (15 mgkg-1) from oral and suppository dosage forms was investigated. Three different combinations of PEG 4000 and 1000 and theobroma oil were used as suppository bases. Oral administration gave higher values for mean residence time (MRT) and absolute bioavailability (F) compared to suppository dosage forms. The theobroma oil base was associated with lower maximum plasma concentration (cpmax), area under the concentration time curve (AUC) and F values compared to the other bases but differences were not significant (P greater than 0.05). Ibuprofen appears to be strongly retained by the lipophilic base, thereby limiting its diffusion through the rectal mucosal membrane. The absorption profile was slightly improved for the three PEG combination bases but were inferior to oral dosing. It is suggested that the relatively smaller size of the rectal mucosal membrane compared to the small intestine was primarily responsible for limiting the rate/extent of ibuprofen absorption. The absorption profile from the suppository preparations may be enhanced by the appropriate selection of the bases and their additives.

Administration, Oral↗
PubMed1991

Concurrent bromosulphophthalein and antipyrine administration to assess liver blood flow and hepatic enzymes in rats.

This study investigated the feasibility of using concurrent iv administration of antipyrine (15 mg/kg body weight) and bromosulphophthalein (BSP; 25 mg/kg) in the rat. Antipyrine is used as an index of hepatic drug metabolism and BSP is used to assess hepatic blood flow. Plasma concentrations of BSP were described using biexponential phases, while antipyrine plasma concentrations were monoexponential. No significant difference was observed between antipyrine pharmacokinetic parameters in concurrent BSP rats when compared with controls. There was also no significant difference between BSP pharmacokinetic parameters in concurrent antipyrine rats when compared with controls, except in the alpha value (P less than 0.05). This indicates that BSP distribution may be affected by concurrent antipyrine administration. Therefore, simultaneous administration of both substrates is not acceptable to study hepatic blood flow. Another iv combination dose (25 mg BSP/kg body weight, followed by 15 mg antipyrine/kg 0.5 hr later) and a dose of 15 mg antipyrine/kg body weight only was administered to rats pretreated with phenobarbital (90 mg/kg body weight) for 6 days. Pharmacokinetic parameters of BSP, beta, k21, k23 and plasma clearance, in the pretreated rats were significantly different from non-pretreated rats. No significant difference was observed in the pharmacokinetic parameters of antipyrine between the combination dose and antipyrine dose in the phenobarbital-pretreated rats. The half-lives of antipyrine in both pretreated groups decreased approximately by 70%, while the clearance increased four times compared with controls. The volume of distribution in these animals did not change as a result of phenobarbital pretreatment. This suggests that a 25 mg BSP/kg body weight dose followed by 15 mg antipyrine/kg 0.5 hr later may be a feasible approach to study liver blood flow, as well as hepatic efficiency in rats.

Animals↗
PubMed1989

Disposition kinetics of cimetidine and ranitidine in endotoxin pretreated rats.

Cimetidine and ranitidine are used in patients with life-threatening gram-negative infections, endotoxemia and acute stress erosions. Disposition kinetics of cimetidine and ranitidine in endotoxin pretreated rats was investigated. The H2-antagonists were administered intravenously 24 h after endotoxin (10 mg/kg) pretreatment. This endotoxin dosage resulted in 50% mortality in rats. Blood samples (0.25 ml) were collected at different timed intervals. No significant differences were observed in plasma clearance, half-life and volume of distribution between endotoxin pretreated and control rats. Cimetidine is eliminated extensively by the renal route in animals and man with metabolism being a minor process. Ranitidine is metabolized to a large extent (70%) in rats, while in humans this represents a minor process. No significant changes in cimetidine and ranitidine disposition parameters in endotoxin pretreated rats were observed. These results suggest that cimetidine and ranitidine may be used in normal dosages in endotoxemia patients since their pharmacokinetic parameters would not be affected under these circumstances.

Animals↗
PubMed1988

The effect of H2-antagonists on the absorption of bupropion in rats.

Bupropion absorption was investigated by oral administration of bupropion alone or in combination with cimetidine or ranitidine to rats. Blood samples were collected before and at 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.5 and 6 h after bupropion administration. The assay of bupropion in plasma was carried out by an HPLC method. Cimetidine or ranitidine did not significantly affect the plasma bupropion concentrations on concurrent administration. No significant differences were observed between area under the curves (AUC)s, maximum plasma concentration, time to peak and the half-life of bupropion among the three groups. These results indicate that neither cimetidine nor ranitidine significantly affects the rate or the extent of bupropion absorption in rats.

Absorption↗
PubMed1984

Tobramycin-furosemide interaction.

A 70-year-old, 75-kg white female with a history of congestive heart failure was admitted with a two-week episode of progressive shortness of breath, increased abdominal distension, and ankle edema. Sputum Gram stains revealed gram-negative bacilli, and the patient was started on a loading dose of tobramycin 150 mg (2 mg/kg) over 30 minutes. The peak tobramycin level was 3.7 micrograms/ml drawn 45 minutes after the infusion was completed. Seven hours after the loading dose infusion, a trough level of 1.5 micrograms/ml was obtained. Based on the Sawchuk-Zaske method, the patient was started on a regimen of tobramycin 180 mg iv q8h. The following day, the patient received furosemide 120 mg iv. The trough and peak levels drawn 30 minutes before and after the fourth dose of tobramycin were 5.3 micrograms/ml and 16.2 micrograms/ml, respectively. The half-life of tobramycin remained relatively constant, while the volume of distribution decreased 40 percent after the administration of furosemide. This case illustrates that moderate doses of furosemide, administered to edematous patients receiving tobramycin, may cause an increase in both peak and trough levels, thus increasing the chances of ototoxicity and nephrotoxicity.

Aged↗
PubMed1983

Aminoglycoside pharmacokinetics on a microcomputer.

The authors describe the use of a microcomputer to evaluate an existing dosage regimen and to determine a new regimen and steady-state peak and trough levels for four aminoglycoside antibiotics--amikacin, gentamicin, kanamycin, and tobramycin. The microcomputer program is based on a one-compartment open pharmacokinetic model for the aminoglycosides. It accounts for patients' sex, age, height, obesity, and ascitic compartment. The program is divided into seven subprograms for each of the four aminoglycosides: (1) steady-state peak and trough levels are predicted, based on serum creatinine for a given dosage regimen; (2) a dosage regimen that conforms to 6, 8, 12, 16, or 24 hours is ascertained, based on serum creatinine; (3) a dosage regimen is determined, on the basis of serum creatinine, for desired steady-state peak and trough levels; (4) a dosage regimen that conforms to 6, 8, 12, 16, or 24 hours is ascertained for given aminoglycoside serum levels; (5) a dosage regimen for desired peak and trough levels is ascertained for given aminoglycoside serum levels; (6) a dosage regimen that conforms to 6, 8, 12, 16, or 24 hours is ascertained from data collected using Sawchuk's and Zaske's method; and (7) a dosage regimen, estimated for desired peak and trough levels, is estimated from data collected using Sawchuk's and Zaske's method.

Adult↗
PubMed1982

Feasibility of using Travenol sets in an IVAC 230 controller.

The feasibility of using Travenol regular and minidrip sets to deliver intravenous solution with IVAC 230 controllers was investigated. Intravariability within Travenol regular sets proved to be negligible. Likewise, intervariability among IVAC controllers is negligible. The least squares fit obtained from drops per minute (dpm) versus flow rate (ml/hr) for Travenol regular sets using dextrose 5% in water was y = 4.50x + 0.8 (r greater than 0.99). Similarly, the least squares fit for sodium chloride 0.9% was y = 4.50x - 0.6 (r greater than 0.99). Therefore, the calculated dpm for the required flow rate for both solutions is similar using Travenol regular sets. Also, no significant difference is found between the drip rate of dextrose 5% in water and sodium chloride 0.9% with Travenol minidrip at 5, 30, and 60 dpms. This study shows that interchangeability of IVAC administration sets with Travenol regular and minidrip sets is possible for dextrose 5% in water and sodium chloride 0.9% solutions.

Feasibility Studies↗
PubMed1980

Pharmacokinetics of ketamine and two metabolites in the dog.

The plasma concentrations of ketamine, N-demethylketamine (I), and the cyclohexene metabolite (II) formed by oxidation of I were determined at various times after rapid i.v. administration of 15 mg of ketamine HCl/kg of body weight to dogs. A pharmacokinetic model that included two compartments for ketamine and one compartment for each metabolite was developed. Ketamine distributed rapidly with (t 1/2)alpha averaging 1.95 min. The apparent volumes of the central and peripheral compartments for ketamine averaged 542 and 1940 ml/kg of body weight, respectively, and the (t 1/2)beta averaged 61 min. The model indicated that 62% of ketamine was transformed to I and that 11% of I was converted to II. The apparent volumes of distribution of I and II averaged 61% and 59% of body weight, respectively. The total body clearances (plasma) of ketamine, I, and II averaged 32.2, 89.4, and 8.54 ml/min/kg, respectively. Plasma protein binding was determined by equilibrium dialysis; it averaged 53.5% for ketamine (concentration range 0.34-19.5 micrograms/ml), 60.3% for I (0.05-19.6 micrograms/ml), and 70.1% for II (0.09-0.58 micrograms/ml). A minimum anesthetic concentration of 3 micrograms ketamine HCl/ml plasma was used with the model to predict that the duration of ketamine anesthesia after an i.m. dose would not be significantly affected if the absorption t 1/2 varied from 0.48 to 31 min. The model also predicted that accumulation of I and II would not interfere with ketamine anesthesia that was prolonged by repeated doses, each dose administered i.v. on termination of anesthesia from the previous dose.

Animals↗
PubMed1979

Pharmacokinetics of ketamine in the horse.

Ketamine HCl was administered IV to xylazine HCl-treated horses. The plasma concentration of ketamine was measured several times after administration of the drug and these data were used to develop a two-compartment pharmacokinetic model. The distribution and the elimination phase half-lives averaged 2.9 and 42 minutes. The volume of the central compartment averaged 212 ml/kg of body weight and the volume of the peripheral compartment was approximately threefold larger. The total body clearance of ketamine averaged 26.6 ml/minute/kg. Plasma protein binding of ketamine averaged 50% over the concentration limits of 0.3 to 20 microgram/ml. The duration of anesthesia from a single 2.2 mg/kg IV bolus dose of ketamine HCl appeared to be determined largely by distribution; 40% of this dose was predicted to remain in the horse at the time of its recovery from anesthesia.

Anesthesia↗
PubMedDate not supplied

Effect of domperidone on cimetidine and ranitidine absorption in rabbits.

Cimetidine and ranitidine absorption were studied after oral administration to rabbits, alone or in combination with oral and intravenous domperidone. Blood samples were collected before and 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.5, and 6.0 h after cimetidine and ranitidine administration. Assays of cimetidine and ranitidine in plasma samples were carried out using HPLC method. Domperidone overall significantly reduced the area under the plasma concentration-time curve (AUC) by approximately 30 per cent for both drugs. However, domperidone had little effect on the maximum plasma concentration (Cmax), the time taken to reach the maximum plasma concentration (Tmax), and the elimination half-life (t1/2) of cimetidine and ranitidine. The results suggest that domperidone affects the extent but not the rate of cimetidine and ranitidine absorption by enhancing gastric emptying.

Administration, Oral↗
PubMedDate not supplied

Effect of bupropion on cimetidine and ranitidine absorption in rats.

Cimetidine and ranitidine absorption were studied in rats, alone or in combination with concurrent but separate bupropion oral administration. Blood samples were collected before and 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.5, and 6.0 h after dosing. In ranitidine-treated rats, an extra blood sample at 8 h was collected. Assays of cimetidine and ranitidine were carried out using a HPLC method. Mean cimetidine plasma concentrations on concurrent bupropion administration at 0.25 and 0.5 h were approximately 2 and 1.5 times compared to the control. Similarly, mean ranitidine plasma concentrations with bupropion combination at 0.25 and 0.5 h were significantly different and approximately 2 and 3 times higher. Time of maximum concentration for cimetidine and ranitidine on combination were reduced to almost half of the control value. However, only the time of maximum concentration for cimetidine showed statistically significant difference. No significant differences were observed between AUCs, maximum concentrations, and half-lives of cimetidine and ranitidine compared to their respective controls. The results suggest that concurrent bupropion administration may affect the rate but not the extent of absorption of cimetidine and ranitidine.

Administration, Oral↗
PubMedDate not supplied

Effect of hepatic and renal dysfunction on disposition of bupropion in rats.

Disposition of bupropion after oral administration was investigated in carbon tetrachloride (CCl4) and gentamicin treated rats. Bupropion exhibits extensive first-pass effect and is mainly cleared by hepatic route. In rats with hepatic damage, maximum plasma concentration (Cmax) was approximately 3 times higher and area under the plasma concentration-time curve up to 6 h (AUC 0-6) and AUC 0-infinity increased on an average 4 and 5 times respectively compared to the control. The half-life was doubled with hepatic dysfunction. These findings suggest that hepatic impairment in rats causes a decrease in first pass effect as well as an increase in the half-life of the drug. Rats with renal impairment, exhibited a significant increase in Cmax, AUC 0-6 and AUC 0-infinity of bupropion approximately 3-fold as compared to the control, no change in half life of the drug was observed. This indicates that rats with renal impairment show less efficient first-pass effect which may lead to increase in systemic bioavailability. The time to peak observed in all treated animals was not significantly different from the control. The percentage of bound bupropion did not differ either in CCl4 or gentamicin treated plasma as compared to the control.

Administration, Oral↗
PubMedDate not supplied

Evaluation of hepatic dysfunction in endotoxin pretreated rats using tolbutamide as a marker.

The pharmacokinetics of tolbutamide (TB) have been studied in endotoxin pretreated rats with the aim of evaluating TB as a marker for endotoxin effects. Endotoxin dose of 10 mg/kg resulted in a 50% rate of mortality. TB was i.v. administered 24 h. after endotoxin dosing. Clearance (Cl) decreased by approximately 2/3 of its value, area under the curve (AUC) and half-life (t1/2) in the pretreated animals were an average 1.5 times the values for the respective controls. Volume of distribution (Vd) increased by 10% approximately. These findings suggest that endotoxin pretreatment may cause hepatic damage by producing a decrease in Cl and an increase in the t1/2 of TB. But, SGOT levels in pretreated animals were not significantly different. This phenomenon may be explained by the increase in plasma protein binding of TB during endotoxin pretreatment, which decreases the free fraction of the drug in plasma available for metabolism. Endotoxin increased tmax of hydroxy-TB, while no change in Cmax was observed. Since tmax is inversely related to the formation and elimination rates of hydroxy-TB, an increase in tmax may be due to the decrease in both elimination rates. No change in Cmax may be due to the decrease in the rate of formation which is equivalent to the decrease in the rate of elimination of hydroxy-TB.

Animals↗