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At least 109 records · Page 6Linked to original sources
PubMed2006

Dose titration to reduce dipyridamole-related headache.

BACKGROUND: Combination of low-dose aspirin and modified-release dipyridamole (ASA+MR-DP) provides a significantly increased benefit in stroke prevention over aspirin alone. However, headaches were reported in more patients receiving dipyridamole-containing agents than in those receiving placebo. We undertook a randomized, double-blind, placebo-controlled trial to evaluate which dosing regimens of ASA+MR-DP have better tolerance. METHODS: This trial randomized 146 patients with a history of ischemic cerebrovascular disease into three groups: placebo (days 1-28), reduced dose (placebo on days 1-4, ASA+MR-DP once daily before bed during days 5-14, and b.i.d. on days 15-28), and regular dose (placebo on days 1-4, and ASA+MR-DP b.i.d. on days 5-28). Using Chinese diary card, headache was assessed as mean cumulated headache (Sigma frequency x intensity/occurrence days x study days) over the study period, and was graded 0-4 according to Cancer Therapy Evaluation Program, Common Toxicity Criteria, Version 2.0. RESULTS: Intent-to-treat patients after randomization was 46 in placebo group, 45, reduced dose, and 49, regular dose. Among commonly reported adverse effects, headache of any grade occurred significantly more in the regular dose group (38.8%), as compared to the other two groups (p < 0.05). Mean cumulated headache was higher (p < 0.05) in the regular dose group than in the reduced group during days 5-14. Of 27 patients who dropped out, 15 (55.6%) were due to headache, which was substantially more in regular dose (8, 53.3%), though the difference was statistically insignificant. CONCLUSIONS: Initial reduced dose treatment with ASA+MR-DP may cause fewer headaches than regular dosing, and seems better tolerated by those susceptible to phosphodiesterase inhibitor-induced headache.

Aged↗
PubMedDate not supplied

Hemodynamic effects of medetomidine in the dog: a dose titration study.

OBJECTIVE: To characterize the hemodynamic effects of medetomidine administered intravenously at doses ranging from 1 to 20 microg/kg, and to determine whether these effects are dose dependent. STUDY DESIGN: Prospective randomized multidose trial. ANIMALS: Twenty-five clinically normal male beagles (5 groups of 5), aged 1 to 4 years and weighing 13.5 +/- 1.7 kg. METHODS: Medetomidine, at a dose of 1, 2, 5, 10, or 20 microg/kg, was administered intravenously at time 0. Heart rate, arterial pressure, central venous pressure, mean pulmonary arterial pressure, pulmonary capillary wedge pressure, body temperature, cardiac output, and packed cell volume were measured immediately before and at selected times after medetomidine administration (3, 7, 10, 20, 30, 40, 50, and 60 minutes in all groups, at 90 minutes for the 10 and 20 microg/kg groups, and at 120 minutes for the highest dose). Cardiac index, stroke index, rate-pressure product, systemic vascular resistance index, pulmonary vascular resistance index, and left and right ventricular stroke work indices were calculated. The degree of sedation was subjectively scored by an observer who was blinded to the treatment used. RESULTS: Heart rate, rate-pressure product, cardiac index, and left and right ventricular stroke work indices decreased below baseline values. Central venous pressure and systemic vascular resistance index increased above baseline measurements. Except in the 2 microg/kg group, after an initial and short lasting increase, a prolonged decrease in arterial pressure was observed. CONCLUSIONS: Hemodynamic changes were observed with the intravenous (IV) administration of medetomidine, at any dose. However, the two lowest doses (1 and 2 microg/kg) produced less cardiovascular depression. CLINICAL RELEVANCE: Medetomidine is an alpha-2 adrenoceptor agonist widely used in dogs, producing sedation, analgesia and cardiovascular depression. When using IV medetomidine, a reduction of the recommended dosage (ie, +/-30 to 40 microg/kg) by up to 6 times did not significantly influence the cardiovascular effects.

Adrenergic alpha-Agonists↗
PubMed1998

Desmopressin for the treatment of nocturnal polyuria in the elderly: a dose titration study.

OBJECTIVE: To evaluate the decrease in nocturnal polyuria and the tolerability of three different doses of oral desmopressin in elderly subjects. SUBJECTS AND METHODS: Subjects were included in the study if they; (i) were healthy and free from medication with possible influence on their diuresis or voiding pattern: (ii) had an increased nocturnal frequency (> or = 2 nocturnal voids, as reported in the pre-screening period); and (iii) had a nocturnal urinary output of > or = 0.9 mL/min. Seventeen men and six women (mean age 68.1, SD 4.7 years) met these criteria and were treated with 0.1, 0.2 and 0.4 mg oral desmopressin given at bedtime, each dose taken for one week on three consecutive weeks. RESULTS: The mean (SD) nocturnal diuresis before treatment was 1.6 (0.7) mL/min, which decreased significantly to 1.1 (0.4) mL/min when 0.1 mg desmopressin was given. A dose of 0.2 mg desmopressin resulted in a further small decrease in the nocturnal diuresis to 0.9 (0.4) mL/min, whereas the 0.4 mg dose produced no additional effect. The reduction in nocturnal diuresis occurred almost exclusively in the group with a nocturnal urinary output of > or =1.3 mL/min. After treatment, diuresis returned to pretreatment levels. There was no change in body weight or in ankle circumference during desmopressin treatment and no serious adverse effects were observed. CONCLUSION: Desmopressin reduces nocturnal diuresis in polyuric elderly subjects and this reduction, occurring with doses of 0.1 mg given at bedtime, does not increase in a dose-dependent way.

Administration, Oral↗
PubMedDate not supplied

A dose-titration trial of guanadrel as step-two therapy in essential hypertension.

The efficacy and safety of low-dose guanadrel sulfate were evaluated in 20 patients with essential hypertension based on seated diastolic blood pressures (SDBP) ranging from 95 to 115 mm Hg despite a trial dosage of hydrochlorothiazide 50 mg/d for up to five weeks. These patients had been resistant to, or intolerant of, one or more step-two antihypertensive drugs in the past (i.e., methyldopa, beta-adrenergic blocking agents, clonidine, or prazosin). The majority of patients demonstrated a satisfactory response (SDBP 95 mm Hg or reduction in SDBP of 10 mm Hg) to guanadrel. Nine patients responded at a low dosage, 10 to 20 mg/d and remained free from adverse effects throughout the study (up to 12 weeks of treatment). Of the remaining 11 patients titrated to higher dosages of guanadrel (30 to 60 mg/d), three had no discernible response while six developed adverse effects. The results of the study suggest that guanadrel has an acceptable benefit-to-risk ratio only when used in low dosages (10 to 30 mg/d) and may be successfully employed as step-two antihypertensive therapy in patients resistant to, or intolerant of, other step-two agents.

Adult↗
PubMed1993

Dose titration study of isradipine in Chinese patients with mild to moderate essential hypertension.

In order to assess the effective dose, tolerability, and safety of isradipine as a monotherapeutic antihypertensive agent for Chinese patients in Taiwan, an open trial was carried out. This study consisted of a 2-week, placebo, run-in period and an 8-week active treatment period, starting with isradipine 1.25 mg twice daily (bid) for the first 4 weeks, followed by 2.5 mg bid if the blood pressure was not normalized (diastole < 90 mmHg). One hundred and one patients (M/F = 48:53) were valid for efficacy analysis. Their age ranged from 30 to 64 years (mean +/- SD, 52 +/- 8). The blood pressure before active treatment was 160 +/- 2/104 +/- 1 mmHg. At the end of treatment period I (week 4), 12-14 hours after the last dose, 38 (37.6%) patients were normalized and 47 (46.5%) subjects responded (diastolic blood pressure reduction > or = 10 mmHg). At week 8, 68 (67.3%) patients were normalized and 79 (78.2%) subjects responded. Isradipine reduced both systolic and diastolic blood pressures within 2 weeks of treatment. There were no significant differences in blood pressure reduction between both genders and among age groups. Safety analysis showed two subjects with severe flushing, dizziness, and palpitation who used the dose of 1.25 mg bid. They withdrew from the study. The adverse reactions of other patients were transient, mild, and tolerable. Most of the side effects were related to vasodilatation, but edema was not found. There was no change in body weight or heart rate, nor any atrioventricular conduction disturbances.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1999

Dose titration of an injectable formulation of lufenuron in cats experimentally infested with fleas.

OBJECTIVES: To identify the lowest single dose of lufenuron injected s.c. that results in a 90% disruption of the flea (Ctenocephalides felis) life cycle for 6 months in cats. ANIMALS: 40 domestic shorthair cats (20 males, 20 females) between 5 and 7 months old. PROCEDURE: Cats were randomly assigned to 1 of 5 eight-cat groups and experimentally infested with C. felis on days -8, -7, -6, and -4. On day 0, cats in the 4 treatment groups were treated with an injectable formulation of lufenuron at doses of 2.5, 5, 10, or 20 mg/kg of body weight, respectively. Control cats received the injectable formulation without lufenuron. Experimental infestations were repeated and flea eggs collected at various intervals for 196 days after treatment. Eggs were placed in media and incubated in an insectary for 28 days to determine effects of injectable lufenuron on egg and larval development. Number of adults that emerged from eggs were compared among groups. RESULTS: Lufenuron injected once at a dose of 10 or 20 mg/kg, but not at 2.5 or 5 mg/kg, resulted in a 90% decrease in number of adult fleas emerging from eggs for 196 days after treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate that control of flea egg and larval development for at least 6 months can be achieved in cats with a single s.c. injection of lufenuron (10 mg/kg). The injectable formulation may provide veterinarians and cat owners an alternative to the tablet formulation of lufenuron.

Animals↗
PubMed2005

An investigation of dose titration with darifenacin, an M3-selective receptor antagonist.

OBJECTIVES: To evaluate the efficacy, tolerability and safety of a flexible-dosing strategy with darifenacin, an M(3)-selective receptor antagonist, in patients with symptoms of overactive bladder (OAB). PATIENTS AND METHODS: In this multicentre double-blind 12-week study, 395 patients (aged 22-89 years; 84% female) with OAB symptoms for >6 months were randomized (2 : 1) and received once-daily treatment with darifenacin controlled-release tablets 7.5 mg (268 patients) or matching placebo (127). After 2 weeks of treatment, the efficacy, safety and tolerability were assessed and the dose increased to 15 mg once daily (pseudo-increase for placebo recipients) if additional efficacy was required by both the patient and physician. In the week before clinic visits (at 2 and 12 weeks), patients recorded incontinence episodes (primary efficacy endpoint) and several secondary efficacy variables in an electronic daily diary. Safety and tolerability were evaluated from withdrawal rates and adverse-event reports. RESULTS: The treatment groups had comparable baseline characteristics. Similar proportions of darifenacin (59%) and placebo (68%) recipients increased the dose at 2 weeks; at 12 weeks patients on darifenacin (overall group) had a significantly greater reduction in the median number of incontinence episodes per week than had those on placebo, at - 8.2 (-62.9%) and - 6.0 (-48.1%), respectively (P = 0.035). There were also significant improvements in voiding frequency (P = 0.001), bladder capacity (volume voided; P = 0.036), frequency of urgency (P < 0.001), severity of urgency (P = 0.013) and number of significant leaks/week (i.e. incontinence episodes needing a change of clothing or pads, per week; P = 0.010) for darifenacin over placebo. Subset analysis suggested that some patients (those remaining on darifenacin 7.5 mg) were more sensitive to darifenacin than those who increased the dose, based on both efficacy and adverse events. Continued treatment with 7.5 mg for 'sensitive' patients, and an increased dose (to 15 mg) for remaining patients, resulted in comparable outcomes by 12 weeks. The most common treatment-related adverse events were mild-to-moderate dry mouth and constipation, which led to discontinuation in < 3.0% of darifenacin-treated patients and < 1.0% of the placebo group. Central nervous system and cardiovascular adverse events were comparable to those with placebo. CONCLUSIONS: Darifenacin appears to be an effective, well-tolerated and flexible treatment for patients with OAB, allowing individualized dosing according to patient needs.

Adult↗
PubMed1997

Individualized dose titration of growth hormone (GH) during GH replacement in hypopituitary adults.

OBJECTIVE: Until now, GH treatment in GH-deficient adults has employed dose schedules of GH based on body weight or body surface area and has ignored individual responsiveness to GH. This trial has studied the effects of an individualized GH dose adjusted to match a combination of clinical response, normalization of serum IGF-I concentration and body composition. DESIGN AND PATIENTS: Two closely-matched groups, each comprising 30 GH-deficient adults, 38 men and 22 women aged 48 years, were treated with GH for 12 months. The high dose (HD) group received a target dose of 12 micrograms/kg per day and the individualized dose (ID) group received an initial daily GH dose of 0.17 or 0.33 mg per day (0.5 and 1 IU, respectively), independent of body weight, with dose adjustments thereafter. MEASUREMENTS: Serum concentrations of IGF-I, lipoprotein(a), insulin, calcium, intact PTH, osteocalcin and blood glucose were measured. Body composition was determined according to a 4-compartment model using total body potassium and tritiated water as input variables. Total body nitrogen was measured by in vivo neutron activation and total body bone mineral content by dual energy X-ray absorptiometry. RESULTS: At 12 months, the daily dose of GH was 0.55 +/- 0.03 mg and 0.45 +/- 0.03 mg in the HD and ID groups, respectively (P < 0.05). In the HD group, the mean serum IGF-I increased to levels well above the predicted level, while in the ID group the mean serum IGF-I normalized. Side-effects were experienced by 70% of the subjects in the HD group and by 30% in the ID group (P < 0.001). A similar response to GH in terms of body composition, glucose homeostasis, lipoprotein(a) and blood pressure was obtained in both treatment groups. However, the treatment response in terms of serum calcium, intact PTH and osteocalcin was more marked in the HD group. CONCLUSIONS: Similar efficacy, with a lower dose of GH and fewer side-effects, was obtained by considering individual responsiveness to GH as compared to higher doses of GH adjusted to match body weight.

Adolescent↗
PubMed2005

Rapid dose titration of quetiapine for the treatment of acute schizophrenia and acute mania: a case series.

To quickly reduce symptoms and to optimize long-term outcome, patients with an acute episode of schizophrenia or mania require prompt treatment intervention. The atypical antipsychotic quetiapine ('Seroquel') has been approved for the treatment of schizophrenia and manic episodes associated with bipolar disorder. For patients with acute symptoms such as aggression or agitation, higher doses of quetiapine than the recommended initiation schedule are often required. This report presents the tolerability findings from rapid initiation with high-dose quetiapine for eight patients who were consecutively admitted with acute symptoms of schizophrenia (n 5) or mania (n 3). The results from this case series show that quetiapine treatment could be safely titrated at a more rapid rate and to doses greater than that described in the current prescribing information. For most patients, rapid dose escalation was well tolerated; no serious side effects were observed and vital clinical parameters were unchanged; one patient experienced transient somnolence. In conclusion, these results suggest that rapid dose escalation of quetiapine could be a useful treatment approach for acutely ill patients with schizophrenia and bipolar mania in order to improve acute symptoms and support the need for randomized controlled trials. However, dose adjustments should be considered with respect to each patient's individual level of tolerability.

Acute Disease↗
PubMed1997

Two rapid-dose titrations of sertindole in patients with schizophrenia.

The novel antipsychotic sertindole has demonstrated efficacy in psychosis with an extrapyramidal syndrome profile indistinguishable from placebo. Prior trials of sertindole have increased the dose by 4 mg every third day, whereas the present study evaluated the safety and tolerability of two, previously untested, more rapid dose escalation regimens. Sixteen schizophrenic inpatients entered a 4-day, single-blind placebo washout period in two consecutive groups. All patients received sertindole in 4-mg dose increments up to a maximum dose of 24 mg, which was maintained for 5 days. Dose increases were every other day for group 1 (N = 8) and daily for group 2 (N = 8). Adverse events, electrocardiograms, routine laboratory tests, and plasma sertindole concentrations were recorded. No patient was discontinued because of adverse events. The most frequent adverse events were tachycardia upon orthostatic challenge, nasal congestion, dry mouth, and headache; except for dry mouth, the incidence of these was greater in group 2. All cases of tachycardia were asymptomatic. No clinically significant laboratory abnormalities were detected in either group. In conclusion, 4-mg increases of sertindole every other day seems to be safe. Daily titration was, in general, not well tolerated.

Adult↗
PubMed1999

Is initial dose titration of amlodipine worthwhile in patients with mild to moderate hypertension?

Amlodipine, a dihydropyrimidine calcium antagonist, is effective in the treatment of patients with mild to moderate hypertension at doses of 5-10 mg daily. The aim of the study reported here was to determine whether an early increase in dosage of amlodipine provided an advantage in terms of antihypertensive effect. This was a single-blind, randomised study in 115 patients with mild to moderate hypertension (diastolic blood pressure 95-114 mmHg) conducted at 10 centres with two parallel groups. Group I received amlodipine 5 mg once daily for the entire 10-week treatment period, while group II received amlodipine 5 mg once daily for two weeks, with the option to increase the dose to 10 mg once daily were the diastolic blood pressure to exceed 90 mmHg. The dose was increased in 40% of group II patients (20/50). Diastolic and systolic blood pressure decreased steadily until the end of the sixth week of treatment in both groups, with no statistically significant difference between the groups. The response rate (diastolic blood pressure < or = 90 mmHg) at the end of treatment was 84% in both groups. Because there is no advantage in an early increase in dosage of amlodipine in terms of antihypertensive effect, a dose increase should not be considered until after six weeks of treatment at 5 mg once daily.

Amlodipine↗
PubMed1997

Dose titration study of live attenuated varicella vaccine in healthy children. Pennridge Pediatric Associates.

To approximate the effect of prolonged storage on safety and immunogenicity, healthy children were given a single dose of the currently marketed live attenuated varicella vaccine (3625 pfu) or of a partially heat-inactivated vaccine (1125 or 439 pfu). The 3 doses had similar antigen content (attenuated plus inactive virus particles). The vaccine was well tolerated. No significant differences in adverse reactions were observed. Although the seroconversion rates were excellent at each dose (> or = 98%), the higher doses resulted in significantly greater geometric mean antibody titers at 6 weeks (10.5 and 10.6 ELISA U/mL) compared with the 439 pfu dose (5.7 ELISA U/mL), P < or = .01. One year after immunization, differences in antibodies were similar to the 6-week postimmunization results. Results indicate that until the date of expiry, the vaccine's immunogenicity will be preserved and there will be no clinically important changes in type or frequency of adverse events.

Antibodies, Viral↗
PubMed1979

Dose titration of oxfendazole against common nematodes of swine.

Oxfendazole, a benzimidazole carbamate, was administered as a 0.5% feed additive to 88 pigs naturally infected with two to four nematode species. Dose rates of 1.5 mg/kg of body weight, 3.0 mg/kg, 3.75 mg/kg, 4.5 mg/kg, 6.75 mg/kg, or 9.0 mg/kg were 100% efficacious against Oesophagostomum dentatum and 99.2% to 100% effective against Ascaris suum. Dose rates of 4.5 mg/kg, 6.75 mg/kg, and 9.0 mg/kg were 92.7%, 98.9%, and 99.5% effective, respectively, against mixed populations of Metastrongylus apri and M pudendotectus. Results were variable with Trichuris suis infections. Efficacy was based on the number of nematodes recovered at necropsy. Palatability and acceptability of the feed additive were good, and adverse reactions following administration were not observed.

Animals↗
PubMedDate not supplied

Selective serotonin reuptake inhibitor dose titration in the naturalistic setting.

Little information exists regarding the use of selective serotonin reuptake inhibitors (SSRIs) in the naturalistic setting. The Regenstrief Medical Record System was used to analyze the dosing of SSRIs in the outpatient population of an urban teaching hospital. A cohort of 3350 patients was extracted, of whom 2859 had received fluoxetine and 460 sertraline. This cohort received 21,079 prescriptions. (The 31 patients who were prescribed paroxetine were eliminated from further analysis.) The mean daily dose for all patients receiving fluoxetine was 21 +/- 6 mg for the first prescription dispensed and 25 +/- 11 mg for the ninth. For fluoxetine-treated patients with depression included on their computerized medical problem list, the mean daily dose was 21 +/- 6 mg for the first prescription and 26 +/- 12 mg for the ninth. A mean of 5.0% of all patients continuing fluoxetine therapy had their daily dose increased with each prescription refill during the first nine prescriptions. The mean daily dose for all patients receiving sertraline was 59 +/- 28 mg for the first prescription and 117 +/- 66 mg for the ninth. For sertraline-treated patients with depression included on their computerized medical problem list, the mean daily dose was 57 +/- 25 mg for the first prescription and 110 +/- 65 mg for the ninth. A mean of 14.9% of all patients continuing sertraline therapy had their daily dose increased with each prescription refill during the first nine prescriptions. The frequency of sertraline dose increases was 2 to 3 times the rate for fluoxetine. Because increases in daily doses typically result from inadequate control of symptoms of depression, these findings may reflect fluoxetine's greater effectiveness in controlling symptoms during the initial stages of therapy in the naturalistic setting.

1-Naphthylamine↗
PubMed1990

[Dose titration with Euphylong following prior determination of serum concentration in the steady state].

Euphylong is a theophylline preparation with new galenic slow-release design (micropellets in a capsule), developed for daily single-dose administration in the evening. It has been shown that the majority of patients with bronchial asthma, chronic obstructive bronchitis or emphysema who receive a single evening dose of Euphylong have a theophylline serum concentration that remains within the therapeutic range for 24 hours when the theophylline serum concentration measured at 8 a.m. under steady-state conditions is found to lie within the therapeutic range.

Adult↗
PubMed1995

Antihypertensive efficacy of optimally titrated doses of once-daily sustained-release diltiazem: a placebo-controlled trial. DILPLACOMP Study Group.

This study assessed once-daily sustained-release (o.d. SR) diltiazem in essential hypertension; 158 patients with supine diastolic blood pressures (BP) of 95-115 mm Hg were randomized to 200 mg diltiazem or placebo, then optimally titrated, at 2-week intervals, to 200, 300 or 400 mg to achieve supine diastolic BP < 90 mm Hg or a > or = 10 mm Hg fall from baseline. BP was measured at trough level, 24 h after dosing. After 2 weeks at the dose of 200 mg, supine diastolic BP was significantly reduced (from 101 to 92 mm Hg) compared with placebo (from 101 to 98 mm Hg; p < 0.001), and yielded 57% of responders with diltiazem against 22% with placebo (p < 0.001). Titration allowed supine diastolic BP normalization with diltiazem (88 mm Hg) compared with placebo (93 mm Hg; p < 0.001) and yielded 78% of responders with diltiazem against 37% with placebo (p < 0.01). The safety profile was similar to placebo. 200 and 300 mg o.d. SR diltiazem formulations enable safe and close regimen adjustments in mild-to-moderate essential hypertension.

Adult↗