Extravascular Routes Research Articles

Effects of administration route on valproate pharmacokinetics in the rabbit

The absorption of sodium valproate was studied in 5 rabbits. Each animal received the drug (70 mg/kg) via 3 routes: intravenous, gastric and duodenal. For the 2 extravascular routes, the absolute bioavailability F, maximal plasma concentrations Cmax, times to peak Tmax and absorption coefficients Kabs were the same. Absolute bioavailability was always close to unity. This indicated that valproic acid was absorbed from the intestine as well as from the whole gastrointestinal tract. The other pharmacokinetic parameters such as terminal plasma half-life, total clearance and volume of distribution remained unchanged whatever the route of administration.

Pharmacokinetics of Recombinant Human Erythropoietin in Children with Renal Failure

The single-dose pharmacokinetics of recombinant human erythropoietin (rHuEpo; 40 units/kg1) were investigated in children (9-16 years) with end-stage renal failure. After an intravenous (i.v.) dose, serum rHuEpo concentrations declined in a monoexponential manner with a mean half-life (t1/2) of 5.6 +/- 3 h (+/- SEM; n = 9). Serum clearance and the apparent volume of distribution were estimated to be 10.1 +/- 0.9 ml h-1 kg-1 and 79.5 +/- 5.0 ml kg-1 (n = 9) respectively. Subcutaneous (s.c.) delivery resulted in serum values that peaked at 10 h, and thereafter concentrations declined slowly with a t1/2 of 21.1 +/- 4.5 h (n = 9). Serum rHuEpo concentrations were maximal at 14 h after i.p. administration and the t1/2 was 9.5 +/- 1.0 h (n = 3). The mean fraction absorbed of SC rHuEpo was 0.40 whereas after i.p. administration this fraction was only 0.17. These results show that after both s.c. and i.p. delivery, disposition of the hormone is rate-limited by absorption, and bioavailability for these extravascular routes is poor. In addition, comparison of the results with those available for adults indicates that rHuEpo is better absorbed but more rapidly cleared in children.

Pharmacokinetics of chloramphenicol in sheep after intravenous, intramuscular and subcutaneous administration

The pharmacokinetics of chloramphenicol were studied in sheep after 3 single intravenous (IV), intramuscular (IM) and subcutaneous (SC) administrations (30 mg/kg). The two extravascular routes were studied during a crossover trial for a bioequivalence test. After IV and SC administrations, the plasma-concentration time graphs were characteristic of a two-compartment model, and after IM administration it was characteristic of a monocompartment model. The two routes of absorption were not bioequivalent. Using the kinetic values, multidose regimens to maintain the therapeutic chloramphenicol blood level (5 micrograms/ml) were proposed: 60 mg/kg every 12 hours for 72 hours for the IM administration and 45 mg/kg administered subcutaneously according to the same regimen. A study of the chloramphenicol residues in tissues was carried out. Chloramphenicol residues remained at the injection site, and 400 hours would be necessary to obtain the level of 10 micrograms/kg. Determination of the creatinine phosphokinase serum values showed that the subcutaneous route induced less damage to muscle than the intramuscular route.

Monitoring Irrigating Fluid Absorption During Transurethral Resection of the Prostate (Turp); A Comparison Between 1 and 2% Ethanol as a Tracer

In a series of 35 transurethral resections of the prostate 1% ethanol was compared to 2% ethanol as a marker of the irrigating fluid. The ethanol concentration in the expired breath of the patient (EB-ethanol) correlated significantly to the irrigant absorption, as measured volumetrically, and to the change in the serum sodium concentration at 10-min intervals during the operation. The pattern of changes in EB-ethanol indicated whether the main part of the absorption entered through the intravenous or the extravascular route. With 1% ethanol added to the irrigating solution the absorption of 100-150 ml in 10 min could readily be detected. The sensitivity was twice as great with 2% ethanol; however, 1% ethanol is sufficient for routine procedures as it permits absorption to be detected long before it is large enough to produce a TUR syndrome. Monitoring ethanol in the expired breath provides the surgeon with an instrument to check that preventive steps against further absorption are effective.

Pharmacokinetics of a long-acting chloramphenicol formulation administered by intramuscular and subcutaneous routes in cattle.

The pharmacokinetic properties of a long-acting formulation of chloramphenicol were determined in six yearling cattle after a single intravenous (i.v.) administration (40 mg/kg body weight) and after two sequential subcutaneous (s.c.) or intramuscular (i.m.) administrations (90 mg/kg/48 h). The two extravascular routes were studied during a crossover trial for a bioequivalence test. After i.v. administration, the plasma concentration-time graph was characteristic of a two-compartment open model. Mean values were a half-life of 4.1 h, a volume of distribution of 0.86 l/kg and a body clearance of 0.128 l/kg/h. Plasma concentrations of chloramphenicol following i.m. and s.c. administrations increased slowly to a broad peak at 10-15 micrograms/ml between 9 and 12 h. Bioavailability was 19.1% after i.m. injection and 12.4% after s.c. administration. The extent of absorption from the two routes did not differ significantly. The rate of absorption was significantly lower after s.c. application than it was after i.m. injection. The time necessary for the plasma concentration to exceed 5 micrograms/ml was the same for the two routes. Thus, i.m. and s.c. routes are bioequivalent.

The effect of posture on the pharmacokinetics of intravenous benzylpenicillin.

We have studied the pharmacokinetics of intravenously administered benzylpenicillin in normal subjects during bedrest and during ambulation. The values of total body clearance, mean residence time, and renal clearance found during ambulation were 487.4 +/- 100.5 ml/min, 36.23 +/- 13.45 min, and 309.4 +/- 93.4 ml/min (means +/- SD). The corresponding values for bedrest were 543.6 +/- 122.6 ml/min, 35.27 +/- 10.21 min, and 324.1 +/- 145.3 ml/min. There were no significant differences between any of these pharmacokinetic variables with the change in posture. These results differ from previously reported results for the effects of posture on the pharmacokinetics of penicillins administered by extravascular routes, and suggest that the absorption of benzylpenicillin may be dependent on posture.

Simultaneous determination of the intravenous and oral pharmacokinetic parameters of D,L-verapamil using stable isotope-labelled verapamil.

Following i.v. administration, the plasma concentration-time curve of verapamil could best be described by either a mono- or biexponential equation. Total plasma clearance (1.26 1/min) approached liver blood flow (1.51/min), so it can be concluded that its clearance is liver blood flow-dependent. Although absorption was almost complete after oral administration, absolute bioavailability (20%) was low, due to extensive hepatic first-pass metabolism. The approach using stable isotope-labelled and unlabelled drug permits simultaneous administration by the intravascular and extravascular routes, thus allowing determination of absolute bioavailability in a single experiment.

Alternate routes of surgical fluid administration

1. 1. Selected patients undergoing a variety of elective abdominal surgical procedures have been given peritoneal or intestinal balanced salt solutions at the time of surgery in addition to the intravenous fluids used during anesthesia. 2. 2. Postoperative fluid requirements were met by oral and intestinal tube fluid administration. No postoperative intravenous fluids were given. 3. 3. Analysis of functional extracellular fluid volume changes and sodium balance indicated that fluids given by these extravascular routes are comparable in their effects to the same solutions given intravenously. 4. 4. Increased patient comfort and mobility, and greater physiological fluid absorption, argue for increased acceptance of nonintravenous routes of fluid administration by gastrointestinal surgeons.

Effects of reserpine and chlorpromazine in prevention of cerebral edema and reversible cell damage.

Summary1) Serotonin, administered into brain-tissue via an extravascular route, induces edema, possibly due to its musculotropic property. 2) Serotonin was confirmed to have a neurotropic action which appeared to be responsible for the reversible hemiplegic symptoms. 3) The neurotropic effect of serotonin is biphasic, i.e. when administered in low dosage via internal-carotid artery, it causes transient spastic paralyses. In high dosage, it causes flaccid paralyses without inducing cerebral edema. 4) Chlorpromazine and reserpine both block the edemainducing action of serotonin. Reserpine is, however, effective in a much lower dosage. 5) Chlorpromazine potentiates the neurotropic depressant effect of serotonin, but apparently does not alter its stimulating action. 6) Reserpine inhibits the neurotropic effect of serotonin. This holds true for the spastic as well as for the flaccid symptoms. 7) Therapeutic considerations suggest that reserpine may be specifically indicated in prophylactic treatment of apoplexy.

A clinically significant steroidogenic assay of corticotropin (ACTH) administered extravascularly to human subjects and to guinea pigs.

In developing what was to become the official method for assaying corticotropin (ACTH) preparations, Sayers, Sayers, and Woodbury (1948) found that more uniform results were obtained during their assays if the ACTH was administered intravenously rather than by extravascular routes. Thus, when ACTH came into clinical use the potencies of various clinical preparations were assayed in terms of their capacity, when administered intravenously to hypophysectomized rats, to cause depletion of adrenal ascorbic acid content. Most of the ACTH administered clinically, however, has been given by the intramuscular route. Soon after the introduction of ACTH into clinical medicine it was reported by Gordon, Kelsey, and Meyer (1951) that the available ACTH preparations were many times more potent, judged by clinical indices, when administered as prolonged intravenous infusions than when administered intramuscularly. It then became apparent from the studies of Forsham, Renold, and Frawley (1951)

THE FATE OF SUBCUTANEOUSLY INJECTED RED BLOOD CELLS

<h3>PART I.</h3> Modern methods of intravenous transfusion are so satisfactory that today the question of using an extravascular route arises in infants only. A study of the older writings shows that at different times and places both the subcutaneous and intraperitoneal routes were employed and in the opinions of the reporters usually with success. My interest in the subject arose from observations made on two patients who were injected subcutaneously after unsuccessful attempts at intravenous transfusion. One of the patients, whose cells were never greatly diminished, showed a decided rise in hemoglobin, and the second patient showed a marked rise in both hemoglobin and cells. Unfortunately for the experiment, however, both patients were given iron. I then purposely employed the subcutaneous rather than the intravenous route in three patients who received no drug. The blood was citrated. With the exception of Ann F., who was given blood from her mother,