Biomedical subjects

M R Vasko

Publications and source records attributed to M R Vasko.

At least 37 records · Page 2Linked to original sources

PubMed1994

Prostacyclin enhances the evoked-release of substance P and calcitonin gene-related peptide from rat sensory neurons.

Prostacyclin (PGI2) is a potent prostanoid producing various symptoms of inflammation, including an increased sensitivity to noxious stimulation. One component of these PGI2-mediated actions may involve activation or sensitization of sensory neurons to enhance release of neuroactive peptides. We, therefore, examined whether PGI2 and carba prostacyclin (CPGI2), a stable analog of PGI2, could alter the resting and evoked release of the neuropeptides, substance P (SP) and calcitonin gene-related peptide (CGRP) from embryonic rat sensory neurons grown in culture. Treating isolated sensory neurons with CPGI2 (10-1000 nM) for 30 min caused a 3-fold increase in the resting release of both peptides. One nM CPGI2, a concentration that did not alter the resting release, significantly enhanced neuropeptide release evoked by capsaicin, 100 nM bradykinin, or 40 mM KCl. Similarly, 10 nM PGI2 did not alter resting release, but augmented capsaicin-stimulated release of SP and CGRP 2-3 fold. In contrast, prostaglandin F2 alpha was ineffective in altering either resting or capsaicin-evoked peptide release. Our results demonstrate that low concentrations of PGI2 sensitize sensory neurons to other stimuli, whereas higher concentrations evoke release directly. This PGI2-induced augmentation of neuropeptide release may be one mechanism contributing to neurogenic inflammation.

Animals↗

PubMed1994

The phosphatase inhibitor, okadaic acid, increases peptide release from rat sensory neurons in culture.

We examined the effects of the phosphatase inhibitor, okadaic acid, on substance P and calcitonin gene-related peptide release from embryonic rat sensory neurons grown in culture. Exposing isolated sensory neurons to 500 or 1000 nM okadaic acid for 30 min resulted in a 2- to 5-fold increase in the release of either peptide above resting levels and this evoked release was dependent on extracellular calcium. Treating sensory neurons with 250 nM okadaic acid did not alter resting peptide release, but significantly enhanced peptide release evoked by either 50 nM capsaicin, 100 nM bradykinin, or 30 mM KCl. These results suggest that enhancing phosphorylation in sensory neurons is an important component in augmenting transmitter release.

Animals↗

PubMed1994

Endothelin-1 enhances capsaicin-induced peptide release and cGMP accumulation in cultures of rat sensory neurons.

Because endothelin-1 (ET-1) may be a neuromodulator in sensory systems, we examined whether this peptide could alter release of substance P (SP) and calcitonin gene-related peptide (CGRP) from isolated sensory neurons. Although ET-1 had minimal actions on spontaneous neuropeptide release, pretreating cultures with 500 nM resulted in a 50% augmentation of SP and CGRP release evoked by 50 nM capsaicin. Moreover, 2000 nM ET-1 enhanced capsaicin-evoked release of CGRP two fold. In an analogous manner, ET-1 alone did not alter intracellular cGMP content, but enhanced the increase in cGMP caused by 50 nM capsaicin. Intracellular cAMP was not altered by capsaicin and/or ET-1. These data suggest that ET-1 may play a role in modulation of peptide release from primary afferent neurons.

Animals↗

PubMed1994

Nitric oxide and cyclic guanosine 3',5'-monophosphate do not alter neuropeptide release from rat sensory neurons grown in culture.

Recent studies demonstrate that nitric oxide and cyclic guanosine 3',5'-monophosphate may mediate hyperalgesia induced by N-methyl-D-aspartate at the level of the spinal cord. One possible mechanism for this action is that nitric oxide increases transmitter release from the primary afferent nociceptors that synapse in the dorsal horn of the spinal cord. To address this possibility, we investigated whether various nitric oxide donors and cyclic guanosine 3',5'-monophosphate could alter the release of substance P and calcitonin gene-related peptide from rat sensory neurons in culture. Sodium nitroprusside (100 nM to 100 microM) had little effect on basal release of either peptide, but it significantly increased the release of substance P and calcitonin gene-related peptide induced by 50 nM capsaicin. In contrast, sodium nitroprusside did not alter release evoked by 100 nM bradykinin or 30 mM KCl. Two other nitric oxide-donating compounds, S-nitroso-N-acetylpenicillamine and 3-morpholinosydnonimine did not enhance resting or capsaicin-evoked peptide release, although they induced a marked elevation in the intracellular cyclic guanosine 3',5'-monophosphate levels. Pretreating the cultures with 8-bromo-cyclic guanosine 3',5'-monophosphate, (0.5 or 0.1 mM for 30 or 60 min) did not result in the enhancement of capsaicin-induced release from sensory neurons. Moreover, pretreating the cells with the nitric oxide synthase inhibitor, NG-nitro-L-arginine (100 microM), abolished the rise in cyclic guanosine 3',5'-monophosphate induced by capsaicin without altering capsaicin-stimulated release of either peptide.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Prostaglandin E2 enhances bradykinin-stimulated release of neuropeptides from rat sensory neurons in culture.

Prostaglandins are known to enhance the inflammatory and nociceptive actions of other chemical mediators of inflammation such as bradykinin. One possible mechanism for this sensitizing action is that prostanoids augment the release of neuroactive substances from sensory neurons. To initially test this hypothesis, we examined whether selected prostaglandins could enhance the resting or bradykinin-evoked release of immunoreactive substance P (iSP) and/or immunoreactive calcitonin gene-related peptide (iCGRP) from sensory neurons in culture. Bradykinin alone causes a concentration-dependent increase in the release of iSP and iCGRP from isolated sensory neurons, and this action is abolished in the absence of extracellular calcium. Pretreating the neurons with PGE2 (10 nM to 1 microM) potentiates the bradykinin-evoked release of both iSP and iCGRP by approximately two-to fourfold. At these concentrations, PGE2 alone did not significantly alter peptide release. Exposing the cultures to 1 microM PGF2 alpha is ineffective in altering either resting or bradykinin-evoked peptide release. Sensory neurons in culture contain cyclooxygenase-like immunoreactivity suggesting that the enzyme that converts arachidonic acid to prostaglandins is present. In addition, pretreating cultures with 14C-arachidonic acid yields radiolabeled eicosanoids that cochromatograph with known prostaglandin standards. Preexposing cultures to indomethacin abolishes the production of prostaglandins and attenuates the bradykinin-stimulated release of iSP and iCGRP. This implies that the synthesis of prostaglandins contributes to the bradykinin-evoked release of peptides. The augmentation of bradykinin-induced release of iSP and iCGRP by PGE2 may be one mechanism to account for the inflammatory and hyperalgesic actions of this eicosanoid.

Animals↗

PubMed1992

Prostaglandin E2 increases calcium conductance and stimulates release of substance P in avian sensory neurons.

Prostaglandins are known to lower activation threshold to thermal, mechanical, and chemical stimulation in small-diameter sensory neurons. Although the mechanism of prostaglandin action is unknown, agents known to elevate intracellular calcium produce a sensitization that is similar to that produced by prostaglandins. Consistent with the idea of prostaglandin-induced elevations in calcium, prostaglandins might also stimulate the release of neurotransmitter from sensory neurons. We therefore examined whether prostaglandin E2 (PGE2) could enhance the release of the putative sensory transmitter substance P (SP) from isolated neurons of the avian dorsal root ganglion grown in culture. Utilizing the whole-cell patch-clamp recording technique, we also examined whether PGE2 could alter calcium currents in these cells. Exposure of sensory neurons to PGE2 produced a dose-dependent increase in the release of SP. One micromolar PGE2 increased release approximately twofold above basal release, whereas 5 and 10 microM PGE2 increased release by about fourfold. The release evoked by these higher concentrations of PGE2 was similar in magnitude to the release induced by 50 mM KCl. Neither arachidonic acid (10 microM), prostaglandin F2 alpha (10 microM), nor the lipoxygenase product leukotriene B4 (1 microM) significantly altered SP release. The addition of 1 microM PGE2 increased the peak calcium currents by 1.8-fold and 1.4-fold for neurons held at potentials of -60 and -90 mV, respectively. The action of PGE2 was rapid with facilitation occurring within 2 min. As with release studies, arachidonic acid, prostaglandin F2 alpha, and leukotriene B4 had no significant effect on the amplitude of the calcium current. These results suggest that PGE2 can stimulate the release of SP through the activation or facilitation of an inward calcium current. The capacity of PGE2 to facilitate the calcium current in these sensory neurons may be one mechanism to account for the ability of prostaglandins to sensitize sensory neurons to physical or chemical stimuli.

Animals↗

PubMed1991

Inhibitory effects of clonidine and tizanidine on release of substance P from slices of rat spinal cord and antagonism by alpha-adrenergic receptor antagonists.

Effects of clonidine and tizanidine, which have antinociceptive and alpha 2-agonistic actions, were studied on the release of substance P from slices of spinal cord from the rat. Veratridine-evoked depolarization induced a 2-3-fold increase in the release of substance P from the slices of spinal cord. Exposure of the cord tissue to 10 microM clonidine and tizanidine significantly reduced the release of substance P. The inhibitory effects of clonidine and tizanidine were attenuated by pre-exposure of the tissue to 10 microM piperoxane, which has alpha 2-antagonistic activity and the inhibitory effect of clonidine was attenuated by 10 microM yohimbine. Moreover, the inhibitory effects of clonidine and tizanidine were also blocked by a small dose of prazosin, an antagonist for alpha 1- and alpha 2B-receptors. None of the antagonists had any effect on release of substance P, when given alone. These results suggest that alpha 2B-adrenoceptors are involved in the inhibitory effects of clonidine and tizanidine on the release of substance P.

Adrenergic alpha-Antagonists↗

PubMed1991

A controlled trial of the cost benefit of computerized bayesian aminoglycoside administration.

We studied the effect of a bayesian pharmacokinetic dosing program on the outcome of aminoglycoside therapy in patients with clinical infections. Patients were randomized to a control (dosing based on physician choice; n = 75) or experimental group (dosing based on the bayesian program; n = 72). Both groups used serum aminoglycoside concentration data when making dosing decisions. Improved response rates were seen in the experimental (60%; 42/68) compared with the control group (48%; 36/68). A higher, but not statistically significant, incidence of toxicity was found in the control (7/75; 9.7%) versus the experimental group (4/72; 5.1%). Mean length of total hospital stay was significantly longer for patients in the control group (20.3 days) compared with the experimental group (16.0 days) (p = 0.028). The variables from multivariate analysis with a significant impact on length of stay were patient group and length of aminoglycoside therapy. On the basis of a reduced length of stay, a potential cost savings of $1311 per patient can be achieved.

Aminoglycosides↗

PubMed1991

In vitro release of endogenous dopamine from the striatum of the weaver mutant mouse.

The weaver mutant mouse has a genetically determined defect in the nigrostriatal dopaminergic system. The present study was undertaken to test the hypothesis that in the weaver mutant mouse, striatal nerve terminals undergo compensatory changes in response to this deficiency. To test this hypothesis, we studied the basal and stimulated release of dopamine from striatal slices of weaver mutant mice and matched controls. By using a superfusion system and concentrating the superfusate by passage over alumina, resting dopamine release could be determined in the weaver mutant despite the fact that striatal tissue content of dopamine in these mice is reduced by greater than 75% compared with control mice. Fractional resting release of dopamine in weaver striatal slices was significantly elevated compared with that in controls, suggesting that the release mechanisms in the weaver may be adapting to overcome the dopamine deficit. Potassium-evoked release (24 and 48 mM potassium) was not significantly different between the two genotypes. In contrast, amphetamine-evoked release (1 microM) was significantly greater in the weaver mice than in controls. In both genotypes, release evoked by amphetamine was completely inhibited by cocaine, implicating the dopamine uptake carrier in this release process. These findings suggest that fundamental differences in dopamine release mechanisms exist between weaver and control mice and support the hypothesis that compensatory mechanisms may develop in neurons in response to dopamine deficits.

Amphetamine↗

PubMed1990

gamma-Aminobutyric acid inhibits the potassium-stimulated release of somatostatin from rat spinal cord slices.

Evidence supports the idea that somatostatin (SO) is a neurotransmitter or neuromodulator of primary afferent neurons involved in nociception. Since gamma-aminobutyric acid (GABA), norepinephrine, and morphine alter nociception at the level of the spinal cord, we examined whether these agents could alter the potassium-stimulated release of somatostatin from rat spinal cord slices. Male Sprague-Dawley rats were decapitated and a 2 cm segment of the lumbar spinal cord removed and chopped into 0.5 x 0.5 mm pieces and perfused at 37 degrees C in individual perfusion chambers with a modified Krebs-bicarbonate buffer at a flow rate of 0.5 ml/min. Perfusates were collected at 2 min intervals and assayed for SO using radioimmunoassay. Exposure of spinal cord tissue to 50 mM KCl resulted in a 3-fold increase in release of SO from a basal level of approximately 0.2 to 0.6 pg/mg tissue/min. This evoked release was calcium dependent. Pre-exposure of tissue to GABA at 10(-4) and 10(-5) M significantly inhibited the potassium-stimulated release of SO, but did not alter basal release. The GABA receptor antagonist, bicuculline methiodide, at 10(-5) but not 10(-6) M attenuated the GABA-induced inhibition of somatostatin release. Bicuculline methiodide alone did not significantly alter either basal or stimulated release. Neither baclofen (10(-5) M, 5 x 10(-5) M), norepinephrine (10(-5) M), nor morphine (10(-5) M) had any significant effect on basal or stimulated release of SO from spinal cord tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Adenosine analogs do not inhibit the potassium-stimulated release of substance P from rat spinal cord slices.

Adenosine agonists produce antinociception when injected directly onto the spinal cord of rats and mice. One mechanism to account for this effect could be inhibition of neurotransmitter release from nociceptive sensory neurons. Consequently, we studied whether these agents could inhibit the potassium stimulated release of one such transmitter, substance P, from rat spinal cord slices. A 2 cm section of lumbar spinal cord was dissected from male Sprague-Dawley rats, chopped into 0.5 x 0.5 mm sections and perfused at 37 degrees C with a modified Krebs bicarbonate buffer containing either 3.5 mM, 30 mM, or 50 mM KCl in the presence and absence of various adenosine analogs. Perfusates, collected every 2 min, were assayed for substance P by radioimmunoassay. Exposure of tissue to 50 mM KCl produced an approximate three-fold increase in the release of substance P over basal release. This increase in release was calcium dependent. Perfusion of spinal cord tissues with either adenosine (10(-3) M). N6-cyclohexyladenosine (10(-5) M or 5 x 10(-5) M), 5'-N-ethylcarboxamide adenosine (10(-5) M) or L-N6-phenylisopropyladenosine (10(-5) M) did not significantly alter basal or potassium-stimulated release of SP when compared to controls. In contrast to the adenosine agonists, exposure of the spinal cord tissue to 10(-5) M morphine significantly reduced the potassium-stimulated release of substance P. Pretreatment of the slices with 10(-5) M theophylline or 8-phenyl-theophylline did not significantly attenuate the inhibition of substance P release produced by morphine. Theophylline alone (10(-5) M) had no significant effect on either basal or potassium-stimulated release of SP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

PubMed1990

Transient potassium currents in avian sensory neurons.

1. We used the patch-clamp technique to study voltage-activated transient potassium currents in freshly dispersed and cultured chick dorsal root ganglion (DRG) cells. Whole-cell and cell-attached patch currents were recorded under conditions appropriate for recording potassium currents. 2. In whole-cell experiments, 100-ms depolarizations from normal resting potentials (-50 to -70 mV) elicited sustained outward currents that inactivated over a time scale of seconds. We attribute this behavior to a component of delayed rectifier current. After conditioning hyperpolarizations to potentials negative to -80 mV, depolarizations elicited transient outward current components that inactivated with time constants in the range of 8-26 ms. We attribute this behavior to a transient outward current component. 3. Conditioning hyperpolarizations increased the rate of activation of the net outward current implying that the removal of inactivation of the transient outward current allows it to contribute to early outward current during depolarizations from negative potentials. 4. Transient current was more prominent on the day the cells were dispersed and decreased with time in culture. 5. In cell-attached patches, single channels mediating outward currents were observed that were inactive at resting potentials but were active transiently during depolarizations to potentials positive to -30 mV. The probability of channels being open increased rapidly (peaking within approximately 6 ms) and then declined with a time constant in the range of 13-30 ms. With sodium as the main extracellular cation, single-channel conductances ranged from 18 to 32 pS. With potassium as the main extracellular cation, the single-channel conductance was approximately 43 pS, and the channel current reversed near 0 mV, as expected for a potassium current. 6. We conclude that the transient potassium channels mediate the component of transient outward current seen in the whole-cell experiments. This current is a relatively small component of the net current during depolarizations from normal resting potentials, but it can contribute significant outward current early in depolarizations from hyperpolarized potentials.

Animals↗

PubMed1989

Clinical utility of a Bayesian dosing program for phenytoin.

We performed two studies to assess the clinical utility of a Bayesian regression analysis computer program for phenytoin (PHT). In a randomized prospective study of 40 epileptic patients, the dosing program was significantly more accurate (p = 0.002) and less biased (p = 0.02) than a group of physicians at hitting a target PHT serum-concentration. Initial serum PHT concentrations that were not steady state were associated with the largest dosing errors by physicians but did not affect the accuracy of the dosing program. In a second study, we used the dosing program to predict 91 serum concentrations in 31 patients with PHT toxicity after the drug was stopped (initial concentration 26-69 micrograms/ml). The program predicted serum concentrations with a mean error of 3.49 +/- 0.29 micrograms/ml without significant tendency to over- or underpredict. We conclude that this dosing program may aid clinicians by improving dosing accuracy and predicting serum concentrations in patients with PHT toxicity.

Adolescent↗

PubMed1989

Evaluation of a Bayesian method for predicting vancomycin dosing.

The purpose of this study is to evaluate the performance of a vancomycin dosing program in predicting dosages necessary to achieve desired serum vancomycin concentrations in a relatively large patient population. With the completion of initial performance evaluation, revised pharmacokinetic parameter estimates derived in the initial evaluation are used to reevaluate program performance. The program uses population estimates of vancomycin's volume of distribution (Vd) and clearance (Cl) to initially predict dosing, then individualizes those estimates by a Bayesian algorithm (iterations) which uses dosing and the resulting serum vancomycin concentration data. Use of the Bayesian forecaster with one iteration significantly increases the calculated Cl value as compared with population estimates; two and three iterations significantly increase both Vd and Cl when compared with population estimates. Absolute values of the predicted minus observed peak serum vancomycin concentrations (accuracy) are 17.7 +/- 14.0, 6.1 +/- 3.6, and 3.4 +/- 2.1 mg/L for dosing using population estimates, Bayesian with one iteration, and Bayesian with two iterations, respectively. Similarly, accuracy of predictions for trough concentrations is 13.8 +/- 12.4, 3.5 +/- 3.2, and 3.2 +/- 2.6 mg/L for each method, respectively. Bias of dosing predictions in achieving desired peak and trough serum vancomycin concentrations is also significantly reduced by using the Bayesian algorithm. Use of the mean Vd and Cl values from three iterations as the starting parameters in a new group of 12 patients significantly improves program performance when compared with use of initial population parameters. Time of sampling for peak serum concentrations has no effect on program performance. In patients with impaired renal function, use of population estimates resulted in less accurate dosing prediction, but this less accurate performance was not observed with use of the Bayesian forecaster. These data demonstrate the accuracy and lack of bias in individualized dosing predictions using the Bayesian dosing method and the ability of revised pharmacokinetic parameter estimates to improve performance.

Bacterial Infections↗

PubMed1987

Morphologic and functional changes in sympathetic nerve relationships with pancreatic alpha-cells after destruction of beta-cells in rats.

Insulin-dependent diabetes mellitus (IDDM) in humans is accompanied by an attenuation of the response of glucagon to hypoglycemia. To identify an animal model of IDDM with alpha-cell unresponsiveness to glucopenia in which to pursue morphologic and in vitro functional investigation of the lesion, pancreases isolated from rats with IDDM induced by streptozocin (STZ) or occurring spontaneously in BB/W rats were perfused with buffer containing 150, 25, and 150 mg/dl of glucose. In both forms of IDDM the normal glucagon rise during glucopenia was markedly impaired, suggesting an abnormality comparable to that of human IDDM. Studies of the insular sympathetic apparatus were conducted in these rat models. Electron-microscopic examination of peri-insular nerve endings disclosed no discernible abnormality in either form of rat IDDM. However, morphometric analysis of contacts between [3H]norepinephrine-labeled sympathetic nerve terminals and alpha-cells in pancreases from STZ-induced diabetic (STZ-D) rats revealed a 65-70% reduction in direct contacts. An 80% reduction in the number of nerve endings (not labeled) in direct contact with alpha-cells was also noted in the BB/W diabetic rats. Norepinephrine reuptake, studied only in the STZ-D group, was not impaired. The availability of local endogenous norepinephrine to alpha-cells and their sensitivity to exogenous norepinephrine was determined by perfusing 2, 5, or 10 micrograms/ml of tyramine, a releaser of endogenous norepinephrine, and norepinephrine at a concentration that in pancreases from nondiabetic rats gave a quantitatively similar glucagon response.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

Morphine and norepinephrine but not 5-hydroxytryptamine and gamma-aminobutyric acid inhibit the potassium-stimulated release of substance P from rat spinal cord slices.

We studied whether morphine, norepinephrine (NE), 5-hydroxytryptamine (5-HT) and gamma-aminobutyric acid (GABA) inhibit the potassium-stimulated release of substance P (SP) from rat spinal cord slices. Male Sprague-Dawley rats were decapitated and a 2-cm segment of lumbosacral spinal cord was removed, chopped into 0.5 X 0.5 mm pieces, weighed, placed in a perfusion chamber and perfused at 37 degrees C with a modified Krebs bicarbonate buffer. Perfusate was collected, lyophilized, then assayed for SP using radioimmunoassay. Exposure of spinal cord tissue to 50 mM KCl for 8 min produced a calcium-dependent increase in the release of SP from a basal level of approximately 0.1 pg/mg tissue/min to 0.3 pg/mg tissue/min. Morphine and NE at concentrations of 10(-4) and 10(-5) M did not alter basal release but caused a significant reduction in the potassium-stimulated release of SP. Naloxone (10(-5) M) and phentolamine (10(-5) M) did not affect SP release but attenuated the effects of morphine and NE, respectively. Naloxone did not antagonize the inhibition of release produced by NE nor did phentolamine block the effect of morphine, suggesting that the actions of the agonists are independent. In contrast, 5-HT and GABA at concentrations of 10(-4) M and 10(-5) M did not significantly alter the basal or potassium-stimulated release of SP. These results demonstrate a differential regulation of SP release in the spinal cord and support the hypothesis that morphine and NE may modify nociception, in part, by inhibiting the release of SP in the spinal cord.

Animals↗

PubMed1986

Effect of depletion of spinal cord norepinephrine on morphine-induced antinociception.

We studied whether antinociception produced by injection of morphine into the nucleus reticularis paragigantocellularis (NRPG) or by superfusion onto the spinal cord involved norepinephrine (NE)-containing neurons that descend from brainstem into the spinal cord. Spinal cord NE concentrations were depleted with the neurotoxin, 6-hydroxydopamine, and antinociception was measured following morphine injection into NRPG or onto spinal cord. Depletion of cord NE by approximately 90% did not attenuate the antinociceptive effect of either 2 or 10 micrograms of morphine injected intrathecally. In contrast, the depletion did significantly attenuate the antinociceptive effect of 2.5 micrograms morphine injected bilaterally into the NRPG. These results suggest that NE-containing neurons descending from brainstem nuclei into the spinal cord are not important in the analgesia produced by injecting morphine directly onto the spinal cord but may be involved with analgesia produced by morphine injection into the NRPG.

Animals↗

PubMed1986

Accuracy of Bayesian and Sawchuk-Zaske dosing methods for gentamicin.

The derived pharmacokinetic variable estimates from a Bayesian aminoglycoside dosing program were compared with those from the Sawchuk-Zaske method to determine which variable estimates were the most accurate in fitting the test dose and in predicting subsequent peak and trough serum concentrations. Data on 17 patients with moderately impaired but stable renal function were analyzed. All patients received gentamicin sulfate for treatment of their infections. To determine the individualized variables using the Bayesian program, demographic data, dosing history, and one (midpoint), two (peak and trough), or four serum drug concentrations were entered into the program. The Sawchuk-Zaske method used three serum concentrations determined following a first dose or four concentrations before and after a subsequent dose to derive individualized pharmacokinetic variables. The estimates of pharmacokinetic variables determined using the Bayesian method with one, two, or four serum concentrations did not differ significantly from those obtained using all the available serum concentrations with the Sawchuk-Zaske method. Although the actual numeric differences of prediction, absolute, and squared errors for fitting the test dose were minimal, significant differences were seen. All methods were similar in predicting serum concentrations from continued dosing. For the prediction error from continued dosing, a slight but significant difference was observed with the Bayesian method using one serum concentration when compared with the other methods. The Bayesian method using one, two, or four serum gentamicin concentrations individualized pharmacokinetic variables as well as the Sawchuk-Zaske method.

Aged↗