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Thomas Brandt - One of the best experts on this subject based on the ideXlab platform.

  • Methylprednisolone valacyclovir or the combination for vestibular neuritis
    The New England Journal of Medicine, 2004
    Co-Authors: Michael Strupp, V C Zingler, Viktor Arbusow, Daniel Niklas, Klaus Peter Maag, Marianne Dieterich, S Bense, Diethilde Theil, Klaus Jahn, Thomas Brandt
    Abstract:

    background Vestibular neuritis is the second most common cause of peripheral vestibular vertigo. Its assumed cause is a reactivation of herpes simplex virus type 1 infection. Therefore, corticosteroids, antiviral agents, or a combination of the two might improve the outcome in patients with vestibular neuritis. methods We performed a prospective, randomized, double-blind, two-by-two factorial trial in which patients with acute vestibular neuritis were randomly assigned to treatment with placebo, Methylprednisolone, valacyclovir, or Methylprednisolone plus valacyclovir. Vestibular function was determined by caloric irrigation, with the use of the vestibular paresis formula (to measure the extent of unilateral caloric paresis) within 3 days after the onset of symptoms and 12 months afterward. results Of a total of 141 patients who underwent randomization, 38 received placebo, 35 Methylprednisolone, 33 valacyclovir, and 35 Methylprednisolone plus valacyclovir. At the onset of symptoms there was no difference among the groups in the severity of vestibular paresis. The mean (±SD) improvement in peripheral vestibular function at the 12-month follow-up was 39.6±28.1 percentage points in the placebo group, 62.4±16.9 percentage points in the Methylprednisolone group, 36.0±26.7 percentage points in the valacyclovir group, and 59.2±24.1 percentage points in the Methylprednisolone-plus-valacyclovir group. Analysis of variance showed a significant effect of Methylprednisolone (P<0.001) but not of valacyclovir (P=0.43). The combination of Methylprednisolone and valacyclovir was not superior to corticosteroid monotherapy.

  • Methylprednisolone, Valacyclovir, or the Combination for Vestibular Neuritis
    The New England journal of medicine, 2004
    Co-Authors: Michael Strupp, V C Zingler, Viktor Arbusow, Daniel Niklas, Klaus Peter Maag, Marianne Dieterich, S Bense, Diethilde Theil, Klaus Jahn, Thomas Brandt
    Abstract:

    background Vestibular neuritis is the second most common cause of peripheral vestibular vertigo. Its assumed cause is a reactivation of herpes simplex virus type 1 infection. Therefore, corticosteroids, antiviral agents, or a combination of the two might improve the outcome in patients with vestibular neuritis. methods We performed a prospective, randomized, double-blind, two-by-two factorial trial in which patients with acute vestibular neuritis were randomly assigned to treatment with placebo, Methylprednisolone, valacyclovir, or Methylprednisolone plus valacyclovir. Vestibular function was determined by caloric irrigation, with the use of the vestibular paresis formula (to measure the extent of unilateral caloric paresis) within 3 days after the onset of symptoms and 12 months afterward. results Of a total of 141 patients who underwent randomization, 38 received placebo, 35 Methylprednisolone, 33 valacyclovir, and 35 Methylprednisolone plus valacyclovir. At the onset of symptoms there was no difference among the groups in the severity of vestibular paresis. The mean (±SD) improvement in peripheral vestibular function at the 12-month follow-up was 39.6±28.1 percentage points in the placebo group, 62.4±16.9 percentage points in the Methylprednisolone group, 36.0±26.7 percentage points in the valacyclovir group, and 59.2±24.1 percentage points in the Methylprednisolone-plus-valacyclovir group. Analysis of variance showed a significant effect of Methylprednisolone (P

Michael Strupp - One of the best experts on this subject based on the ideXlab platform.

  • Methylprednisolone valacyclovir or the combination for vestibular neuritis
    The New England Journal of Medicine, 2004
    Co-Authors: Michael Strupp, V C Zingler, Viktor Arbusow, Daniel Niklas, Klaus Peter Maag, Marianne Dieterich, S Bense, Diethilde Theil, Klaus Jahn, Thomas Brandt
    Abstract:

    background Vestibular neuritis is the second most common cause of peripheral vestibular vertigo. Its assumed cause is a reactivation of herpes simplex virus type 1 infection. Therefore, corticosteroids, antiviral agents, or a combination of the two might improve the outcome in patients with vestibular neuritis. methods We performed a prospective, randomized, double-blind, two-by-two factorial trial in which patients with acute vestibular neuritis were randomly assigned to treatment with placebo, Methylprednisolone, valacyclovir, or Methylprednisolone plus valacyclovir. Vestibular function was determined by caloric irrigation, with the use of the vestibular paresis formula (to measure the extent of unilateral caloric paresis) within 3 days after the onset of symptoms and 12 months afterward. results Of a total of 141 patients who underwent randomization, 38 received placebo, 35 Methylprednisolone, 33 valacyclovir, and 35 Methylprednisolone plus valacyclovir. At the onset of symptoms there was no difference among the groups in the severity of vestibular paresis. The mean (±SD) improvement in peripheral vestibular function at the 12-month follow-up was 39.6±28.1 percentage points in the placebo group, 62.4±16.9 percentage points in the Methylprednisolone group, 36.0±26.7 percentage points in the valacyclovir group, and 59.2±24.1 percentage points in the Methylprednisolone-plus-valacyclovir group. Analysis of variance showed a significant effect of Methylprednisolone (P<0.001) but not of valacyclovir (P=0.43). The combination of Methylprednisolone and valacyclovir was not superior to corticosteroid monotherapy.

  • Methylprednisolone, Valacyclovir, or the Combination for Vestibular Neuritis
    The New England journal of medicine, 2004
    Co-Authors: Michael Strupp, V C Zingler, Viktor Arbusow, Daniel Niklas, Klaus Peter Maag, Marianne Dieterich, S Bense, Diethilde Theil, Klaus Jahn, Thomas Brandt
    Abstract:

    background Vestibular neuritis is the second most common cause of peripheral vestibular vertigo. Its assumed cause is a reactivation of herpes simplex virus type 1 infection. Therefore, corticosteroids, antiviral agents, or a combination of the two might improve the outcome in patients with vestibular neuritis. methods We performed a prospective, randomized, double-blind, two-by-two factorial trial in which patients with acute vestibular neuritis were randomly assigned to treatment with placebo, Methylprednisolone, valacyclovir, or Methylprednisolone plus valacyclovir. Vestibular function was determined by caloric irrigation, with the use of the vestibular paresis formula (to measure the extent of unilateral caloric paresis) within 3 days after the onset of symptoms and 12 months afterward. results Of a total of 141 patients who underwent randomization, 38 received placebo, 35 Methylprednisolone, 33 valacyclovir, and 35 Methylprednisolone plus valacyclovir. At the onset of symptoms there was no difference among the groups in the severity of vestibular paresis. The mean (±SD) improvement in peripheral vestibular function at the 12-month follow-up was 39.6±28.1 percentage points in the placebo group, 62.4±16.9 percentage points in the Methylprednisolone group, 36.0±26.7 percentage points in the valacyclovir group, and 59.2±24.1 percentage points in the Methylprednisolone-plus-valacyclovir group. Analysis of variance showed a significant effect of Methylprednisolone (P

William J. Jusko - One of the best experts on this subject based on the ideXlab platform.

  • Pharmacokinetic and pharmacodynamic interactions between diltiazem and Methylprednisolone in healthy volunteers
    Clinical pharmacology and therapeutics, 2002
    Co-Authors: Brent M. Booker, Mindy He Magee, Robert A. Blum, Christian D. Lates, William J. Jusko
    Abstract:

    Objectives The pharmacokinetics and pharmacodynamics after administration of Methylprednisolone alone, diltiazem alone, and both drugs jointly were assessed in healthy volunteers. Methods An unblinded, controlled, fixed-sequence, 2-period study was carried out in 5 healthy white men who received a single dose of intravenous Methylprednisolone, 0.3 mg/kg, on day 2, followed by diltiazem alone, 180 mg, on days 5, 6, and 7, with joint dosing of both drugs on day 8. Methylprednisolone and diltiazem disposition was assessed from plasma concentrations. Pharmacodynamic factors were assessed by plasma cortisol and T-helper and T-suppressor lymphocytes by means of extended indirect response models. Results The clearance of Methylprednisolone was significantly reduced in the presence of diltiazem (25.2 L/h versus 16.8 L/h), resulting in a longer half-life (2.28 hours versus 3.12 hours) and increased area under the plasma concentration-time curve (AUC) (871 ng · h/mL versus 1299 ng · h/mL). The AUC of diltiazem was unchanged in the presence of Methylprednisolone. No significant intrinsic pharmacodynamic differences were observed for Methylprednisolone versus Methylprednisolone-diltiazem. The 50% inhibitory concentration values were 0.446 ng/mL versus 0.780 ng/mL for cortisol, 9.20 ng/mL versus 10.7 ng/mL for T-helper cells, and 18.5 ng/mL versus 20.9 ng/mL for T-suppressor cells (P > .05). Greater net suppression, as indicated by the area between the effect curve and suppression ratios, was observed for the Methylprednisolone-diltiazem combination versus Methylprednisolone alone, which was attributed to reduced elimination of Methylprednisolone. Conclusions Controlled-delivery diltiazem, 180 mg, significantly increased Methylprednisolone AUC and half-life and reduced clearance, lending to greater systemic exposure to the steroid. However, significant differences between 50% inhibitory concentration values for Methylprednisolone when given alone and for Methylprednisolone in combination with diltiazem were not seen, which implies no change in cortisol or cell-trafficking sensitivity in the presence of diltiazem. Clinical Pharmacology & Therapeutics (2002) 72, 370–382; doi: 10.1067/mcp.2002.127944

  • Oral contraceptive effects on Methylprednisolone pharmacokinetics and pharmacodynamics
    Clinical pharmacology and therapeutics, 1996
    Co-Authors: Kathryn L. Slayter, James J Ferry, Elizabeth A Ludwig, Kim H. Lew, Elliott Middleton, William J. Jusko
    Abstract:

    At the Buffalo General Hospital in New York researchers randomly assigned 6 healthy nonobese women 30-36 years old and using a triphasic oral contraceptive (OC) (Triphasil 28 Wyeth-Ayerst Laboratories) to either the baseline phase group or the group receiving an intravenous bolus of Methylprednisolone sodium succinate at a dose of 0.6 mg/kg ideal body weight during the 2-week period after ovulation (i.e. luteal phase). These women were compared with 6 other women who did not use OCs but did receive the same dose of Methylprednisolone. The purpose was to determine whether the adrenosuppressive anti-inflammatory and immunosuppressive effects of Methylprednisolone differ in OC users. OC users experienced slower clearance of Methylprednisolone (33% slower) than controls. This slower clearance rate contributed to a longer elimination half-life for Methylprednisolone (2.2 vs. 1.72 hours; p < 0.05). OC users also had a rate of slower elimination of cortisol than controls (0.180 vs. 0.276 hr-1; p < 0.05). They had higher mean cortisol levels than controls (136 vs. 65 ng/ml). Women who used OCs for suppression of cortisol secretion had a larger value for the concentration of cortisol that suppresses the zero-order production rate by 50% (0.37 vs. 0.11 ng/ml; p < 0.05) suggesting a decreased sensitivity to the effects of Methylprednisolone on cortisol suppression. OC users experienced a greater net suppression of basophils at drug effect than at baseline. Methylprednisolone appeared to have no effect on helper T-cell responses. These findings suggest that OCs inhibit Methylprednisolone metabolism. Since there were inconsistent changes in several responses women can likely receive similar doses of Methylprednisolone irrespective of OC use.

  • The Pharmacokinetics and Pharmacodynamics of Methylprednisolone in Chronic Renal Failure.
    American Journal of Therapeutics, 1994
    Co-Authors: Mark A. Milad, R. Kohli, Elizabeth A Ludwig, William J. Jusko
    Abstract:

    Methylprednisolone (MP) pharmacokinetics and its directly suppressive effects on cortisol secretion, circulating T-cells, and basophils in blood were compared in six chronic renal failure (CRF) subjects and six healthy controls after an IV administration of MP 0.6 mg kg(minus sign1) as the sodium succinate ester. The CRF subjects were studied between hemodialysis treatments. The total clearance of Methylprednisolone sodium succinate (the prodrug) was reduced by 40% in CRF; however, the pharmacokinetics of Methylprednisolone remained unchanged. Methylprednisolone clearance was approximately 280 ml h(minus sign1) kg(minus sign1) and volume of distribution was about 1.1 L kg(minus sign1). Physiological pharmacodynamic models were applied for the immediate effects of MP, based on the premise that receptor binding is followed by rapid suppression of the secretion of cortisol and recirculation of basophils, T-helper cells, and T-suppressor cells, which persist until inhibitory concentrations (IC(50)) of Methylprednisolone disappear. The difference in IC(50) for each pharmacodynamic parameter was not statistically significant, suggesting no difference in the responsiveness of these factors to Methylprednisolone in CRF. As the pharmacokinetics of other corticosteroids are altered in CRF, the lack of pharmacokinetic and pharmacodynamic changes of Methylprednisolone may engender a therapeutic advantage for this corticosteroid in CRF.

  • Gender‐based effects on Methylprednisolone pharmacokinetics and pharmacodynamics
    Clinical pharmacology and therapeutics, 1993
    Co-Authors: Kim H. Lew, Mark A. Milad, James J Ferry, Elizabeth A Ludwig, Elliott Middleton, Kathleen Donovan, William J. Jusko
    Abstract:

    The pharmacokinetics and selected pharmacodynamic responses to Methylprednisolone were investigated in six men and six premenopausal women after a dose of 0.6 mg/kg ideal body weight. Women (luteal phase) exhibited a greater Methylprednisolone clearance (0.45 versus 0.29 L/hr/kg) and shorter elimination half-life (1.7 versus 2.6 hours) than men. The volume of distribution of Methylprednisolone was similar when normalized for ideal body weight. Pharmacodynamic models were used to examine the Methylprednisolone suppressive effects on cortisol secretion and basophil and helper T lymphocyte trafficking. A significantly smaller 50% inhibitory concentration (IC50) value (0.1 versus 1.7 ng/ml) was seen in the women for suppression of cortisol secretion, indicating increased sensitivity. However, the area under the concentration-time curve of effect was similar for both groups. The IC50 values for effects of Methylprednisolone on basophil trafficking related to estradiol concentrations in a log-linear fashion in women, with increased sensitivity found at higher estradiol concentrations. Men displayed a greater 24-hour net suppression in blood basophil numbers, but no difference was observed in net cortisol and helper T lymphocyte suppression between the sexes. These findings suggest that Methylprednisolone dosages should be based on ideal body weight. Although women are more sensitive to Methylprednisolone as measured by cortisol suppression, they eliminate the drug more quickly, generally producing a similar net response.

  • Bioavailability and nonlinear disposition of Methylprednisolone and methylprednisone in the rat.
    Journal of pharmaceutical sciences, 1992
    Co-Authors: David B. Haughey, William J. Jusko
    Abstract:

    Bioavailability of low (10 mg/kg) and high (50 mg/kg) doses of Methylprednisolone was determined after oral administration of the free alcohol of Methylprednisolone and iv administration of Methylprednisolone sodium succinate. Plasma concentrations of Methylprednisolone and methylprednisone (reversible metabolite) were measured by HPLC. Methylprednisolone systemic availability (F) was 49–57% after iv administration and ~35% after oral administration. Solubilization of steroids with PEG:ethanol had no effect on their disposition. Apparent systemic clearance (CL) of Methylprednisolone was 21 mL/min (low dose), approximately twice the liver blood flow. Dose-dependent changes in steady-state volume of distribution (Vdas) and central volume of distribution (Vdc), volumes, and apparent CL were observed. The Methylprednisolone-to-methylprednisone AUC ratio decreased with dose due to saturation of methylprednisone formation clearance (CL12), but this is a minor metabolic pathway. The mean residence time (MRT) increased threefold with dose. Graphical estimates of the Michaelis-Menten capacity(Vmax) and affinity (Km) constants were in reasonable agreement with CL values for the low-dose experimental data. Low systemic availability of iv Methylprednisolone sodium succinate was in part due to sequential first-pass hepatic metabolism of the Methylprednisolone formed. Methylprednisolone disposition is complex in the rat due to extensive first-pass effects, nonlinear elimination, nonlinear distribution, and reversible metabolism.

James J Ferry - One of the best experts on this subject based on the ideXlab platform.

  • Oral contraceptive effects on Methylprednisolone pharmacokinetics and pharmacodynamics
    Clinical pharmacology and therapeutics, 1996
    Co-Authors: Kathryn L. Slayter, James J Ferry, Elizabeth A Ludwig, Kim H. Lew, Elliott Middleton, William J. Jusko
    Abstract:

    At the Buffalo General Hospital in New York researchers randomly assigned 6 healthy nonobese women 30-36 years old and using a triphasic oral contraceptive (OC) (Triphasil 28 Wyeth-Ayerst Laboratories) to either the baseline phase group or the group receiving an intravenous bolus of Methylprednisolone sodium succinate at a dose of 0.6 mg/kg ideal body weight during the 2-week period after ovulation (i.e. luteal phase). These women were compared with 6 other women who did not use OCs but did receive the same dose of Methylprednisolone. The purpose was to determine whether the adrenosuppressive anti-inflammatory and immunosuppressive effects of Methylprednisolone differ in OC users. OC users experienced slower clearance of Methylprednisolone (33% slower) than controls. This slower clearance rate contributed to a longer elimination half-life for Methylprednisolone (2.2 vs. 1.72 hours; p < 0.05). OC users also had a rate of slower elimination of cortisol than controls (0.180 vs. 0.276 hr-1; p < 0.05). They had higher mean cortisol levels than controls (136 vs. 65 ng/ml). Women who used OCs for suppression of cortisol secretion had a larger value for the concentration of cortisol that suppresses the zero-order production rate by 50% (0.37 vs. 0.11 ng/ml; p < 0.05) suggesting a decreased sensitivity to the effects of Methylprednisolone on cortisol suppression. OC users experienced a greater net suppression of basophils at drug effect than at baseline. Methylprednisolone appeared to have no effect on helper T-cell responses. These findings suggest that OCs inhibit Methylprednisolone metabolism. Since there were inconsistent changes in several responses women can likely receive similar doses of Methylprednisolone irrespective of OC use.

  • pilot study of the pharmacokinetics of Methylprednisolone after single and multiple intravenous doses of Methylprednisolone sodium succinate and Methylprednisolone suleptanate to healthy volunteers
    The Journal of Clinical Pharmacology, 1994
    Co-Authors: James J Ferry, Andrew A Dellacoletta, Dennis J Weber, James T Vanderlugt
    Abstract:

    The pharmacokinetics of Methylprednisolone were evaluated in 29 healthy volunteers after multiple intravenous doses of Methylprednisolone sodium succinate or the novel prodrug, Methylprednisolone suleptanate. Subjects were assigned randomly to one of four treatment groups (40, 100, 250, or 500 mg) and then randomly assigned to receive either the sodium succinate or suleptanate prodrugs. Doses were administered every 6 hours for 48 hours. Plasma and urine were assayed for Methylprednisolone and unchanged prodrug using HPLC methods. Methylprednisolone pharmacokinetics exhibited both a dose and time dependency, which was similar for administration of both prodrugs. After first-dose administration, mean clearance increased from 19.5 L/hr for 40-mg doses to 27.7 L/hr after 500-mg doses of the sodium succinate ester, and from 20.1 to 31.7 L/hr after the suleptanate ester. After multiple dosing, mean clearance values increased from 31.1 to 44.7 L/hr for sodium succinate dosing, and from 31.5 to 46.0 L/hr for suleptanate dosing. Apparent systemic clearance values determined after multiple dosing were 1.5- to 1.8-fold greater than corresponding first-dose values. No dependence on time was apparent for any prodrug pharmacokinetic parameter. These data suggest that the dose dependency of Methylprednisolone pharmacokinetics is related to dose-dependent prodrug hydrolysis, whereas the time dependence possibly reflects auto-induction of Methylprednisolone metabolism. Based on comparison of Methylprednisolone pharmacokinetic parameters derived for each prodrug, Methylprednisolone suleptanate resulted in a faster and slightly more efficient conversion to Methylprednisolone than Methylprednisolone sodium succinate.

  • Gender‐based effects on Methylprednisolone pharmacokinetics and pharmacodynamics
    Clinical pharmacology and therapeutics, 1993
    Co-Authors: Kim H. Lew, Mark A. Milad, James J Ferry, Elizabeth A Ludwig, Elliott Middleton, Kathleen Donovan, William J. Jusko
    Abstract:

    The pharmacokinetics and selected pharmacodynamic responses to Methylprednisolone were investigated in six men and six premenopausal women after a dose of 0.6 mg/kg ideal body weight. Women (luteal phase) exhibited a greater Methylprednisolone clearance (0.45 versus 0.29 L/hr/kg) and shorter elimination half-life (1.7 versus 2.6 hours) than men. The volume of distribution of Methylprednisolone was similar when normalized for ideal body weight. Pharmacodynamic models were used to examine the Methylprednisolone suppressive effects on cortisol secretion and basophil and helper T lymphocyte trafficking. A significantly smaller 50% inhibitory concentration (IC50) value (0.1 versus 1.7 ng/ml) was seen in the women for suppression of cortisol secretion, indicating increased sensitivity. However, the area under the concentration-time curve of effect was similar for both groups. The IC50 values for effects of Methylprednisolone on basophil trafficking related to estradiol concentrations in a log-linear fashion in women, with increased sensitivity found at higher estradiol concentrations. Men displayed a greater 24-hour net suppression in blood basophil numbers, but no difference was observed in net cortisol and helper T lymphocyte suppression between the sexes. These findings suggest that Methylprednisolone dosages should be based on ideal body weight. Although women are more sensitive to Methylprednisolone as measured by cortisol suppression, they eliminate the drug more quickly, generally producing a similar net response.

Klaus Peter Maag - One of the best experts on this subject based on the ideXlab platform.

  • Methylprednisolone valacyclovir or the combination for vestibular neuritis
    The New England Journal of Medicine, 2004
    Co-Authors: Michael Strupp, V C Zingler, Viktor Arbusow, Daniel Niklas, Klaus Peter Maag, Marianne Dieterich, S Bense, Diethilde Theil, Klaus Jahn, Thomas Brandt
    Abstract:

    background Vestibular neuritis is the second most common cause of peripheral vestibular vertigo. Its assumed cause is a reactivation of herpes simplex virus type 1 infection. Therefore, corticosteroids, antiviral agents, or a combination of the two might improve the outcome in patients with vestibular neuritis. methods We performed a prospective, randomized, double-blind, two-by-two factorial trial in which patients with acute vestibular neuritis were randomly assigned to treatment with placebo, Methylprednisolone, valacyclovir, or Methylprednisolone plus valacyclovir. Vestibular function was determined by caloric irrigation, with the use of the vestibular paresis formula (to measure the extent of unilateral caloric paresis) within 3 days after the onset of symptoms and 12 months afterward. results Of a total of 141 patients who underwent randomization, 38 received placebo, 35 Methylprednisolone, 33 valacyclovir, and 35 Methylprednisolone plus valacyclovir. At the onset of symptoms there was no difference among the groups in the severity of vestibular paresis. The mean (±SD) improvement in peripheral vestibular function at the 12-month follow-up was 39.6±28.1 percentage points in the placebo group, 62.4±16.9 percentage points in the Methylprednisolone group, 36.0±26.7 percentage points in the valacyclovir group, and 59.2±24.1 percentage points in the Methylprednisolone-plus-valacyclovir group. Analysis of variance showed a significant effect of Methylprednisolone (P<0.001) but not of valacyclovir (P=0.43). The combination of Methylprednisolone and valacyclovir was not superior to corticosteroid monotherapy.

  • Methylprednisolone, Valacyclovir, or the Combination for Vestibular Neuritis
    The New England journal of medicine, 2004
    Co-Authors: Michael Strupp, V C Zingler, Viktor Arbusow, Daniel Niklas, Klaus Peter Maag, Marianne Dieterich, S Bense, Diethilde Theil, Klaus Jahn, Thomas Brandt
    Abstract:

    background Vestibular neuritis is the second most common cause of peripheral vestibular vertigo. Its assumed cause is a reactivation of herpes simplex virus type 1 infection. Therefore, corticosteroids, antiviral agents, or a combination of the two might improve the outcome in patients with vestibular neuritis. methods We performed a prospective, randomized, double-blind, two-by-two factorial trial in which patients with acute vestibular neuritis were randomly assigned to treatment with placebo, Methylprednisolone, valacyclovir, or Methylprednisolone plus valacyclovir. Vestibular function was determined by caloric irrigation, with the use of the vestibular paresis formula (to measure the extent of unilateral caloric paresis) within 3 days after the onset of symptoms and 12 months afterward. results Of a total of 141 patients who underwent randomization, 38 received placebo, 35 Methylprednisolone, 33 valacyclovir, and 35 Methylprednisolone plus valacyclovir. At the onset of symptoms there was no difference among the groups in the severity of vestibular paresis. The mean (±SD) improvement in peripheral vestibular function at the 12-month follow-up was 39.6±28.1 percentage points in the placebo group, 62.4±16.9 percentage points in the Methylprednisolone group, 36.0±26.7 percentage points in the valacyclovir group, and 59.2±24.1 percentage points in the Methylprednisolone-plus-valacyclovir group. Analysis of variance showed a significant effect of Methylprednisolone (P