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Biomedical subjects

D H Wiles

Publications and source records attributed to D H Wiles.

At least 19 recordsLinked to original sources
PubMed1998

Clinical and biochemical determinants of plasma lipid peroxide levels in type 2 diabetes.

The enhanced risk and increased severity of atheroma in diabetes is well recognized but, as yet, incompletely explained. A cross-sectional study of vascular disease risk factors in a group of type 2 diabetic patients from South West Scotland has revealed an association between glycaemic control, assessed by HbAl level and plasma lipid peroxides measured by a specific high-performance liquid chromatography method. Duration of diabetes appeared to be a subsidiary contributor to lipid peroxidation. We suggest this evidence supports the importance of glycaemic control in modulating glyco-oxidative mechanisms probably crucial to production of diabetic complications. Atherosclerosis prevention in diabetes may hinge on exemplary simultaneous control of both hyperglycaemia and hyperlipidaemia.

Chromatography, High Pressure Liquid↗
PubMed1992

The Nithsdale schizophrenia surveys. IX: Akathisia, parkinsonism, tardive dyskinesia and plasma neuroleptic levels.

Of all known schizophrenics living in Nithsdale, south-west Scotland, 146 (88%) were examined for the presence of the three principal movement disorders secondary to antipsychotic medication, namely akathisia, tardive dyskinesia and Parkinsonism. Of these, 18% had akathisia, 5% pseudoakathisia, 29% tardive dyskinesia, 8% persistent tardive dyskinesia, and 27% Parkinsonism. No movement disorder was seen in 445, 36% had one and 20% had more than one movement disorder. Plasma neuroleptic levels at the time of clinical assessment were measured by the radioreceptor technique. Correlations between dose and plasma level were low; the ratio of mean plasma concentration to mean dose was greatest with fluphenazine decanoate and lowest for sulpiride. The concentration:dose ratio was higher in the elderly. There was no relationship between neuroleptic levels and akathisia, Parkinsonism or tardive dyskinesia. Additional psychotropic medication influenced neuroleptic levels. In 9% of patients receiving oral antipsychotic medication, no drug was detected in plasma.

Adult↗
PubMed1990

Pharmacokinetics of haloperidol and fluphenazine decanoates in chronic schizophrenia.

In a double-blind comparison of haloperidol decanoate and fluphenazine decanoate given 4-weekly for 60 weeks as maintenance therapy in 38 chronic schizophrenic in-patients, plasma haloperidol, fluphenazine and prolactin levels were measured at regular intervals by radioimmunoassay. After the first injection, the mean plasma haloperidol level was highest at week 1 and fell gradually towards week 4. Mean pre-dose haloperidol levels changed little after week 8. Results suggested an absorption half-life of 4 weeks, although, in three cases steady state was only achieved after 11 monthly injections. Steady state levels of both haloperidol and fluphenazine correlated highly with dose. In two sub-groups observed at steady state, both drugs produced a biphasic pattern of plasma drug concentration between injections, a rapid rise on day 1 followed by stable elevated levels and a gradual return to pre-injection concentration by the end of week 4. In the fluphenazine sub-group there was a second peak on day 7 and a steeper decline, so that the mean area-under-curve in week 4 was 64% of that in week 1. Drug injections at steady state induced an increase in prolactin secretion in all of the fluphenazine sub-group and in half of those receiving haloperidol. Plasma prolactin changes resembled those for drug concentrations, but differences in times of peaks on day 1 resulted in weak correlations. Fluphenazine appeared more potent than haloperidol in provoking prolactin secretion.

Adult↗
PubMed1987

Haloperidol decanoate v. fluphenazine decanoate as maintenance therapy in chronic schizophrenic in-patients.

In a double-blind study of 38 chronic schizophrenic in-patients, haloperidol decanoate was compared with fluphenazine decanoate as maintenance therapy over 60 weeks. Both drugs were given by injection at 4-week intervals. Haloperidol and fluphenazine were assumed to be equipotent; the mean starting dose of the former was 127 mg and of the latter 106 mg. The number of withdrawals over 60 weeks was similar in both groups but relapses, strictly defined, were significantly more frequent in the haloperidol group. When patients were switched to haloperidol, Parkinsonism diminished more quickly than in the fluphenazine group, but after 60 weeks there was no difference in severity in the two drug groups. The higher relapse rate and the quicker reduction in Parkinsonism in the haloperidol group might be due to a misjudgement in equivalent doses of the two drugs. Plasma haloperidol steady state levels were reached in most patients by 8-12 weeks. Plasma neuroleptic and prolactin levels, week-by-week systemic drug availability and Parkinsonism showed less variation between injections with haloperidol than with fluphenazine.

Adult↗
PubMed1985

Early unwanted effects of fluphenazine esters related to plasma fluphenazine concentrations in schizophrenic patients.

Seven outpatients already receiving neuroleptic drugs by depot intramuscular injections were treated in two consecutive 3-week periods with 25 mg fluphenazine doses as enanthate and decanoate esters in a double-blind crossover study. They were assessed for incidence of akinesia, involuntary movement, autonomic disturbances and drowsiness, using a rating scale, and their blood pressures and pulse rates were recorded. Blood was collected for plasma fluphenazine and plasma prolactin assay. Additionally, a handwriting test was applied. A higher incidence of unwanted drug effects occurred when plasma fluphenazine concentrations were maximal, but this was not so with prolactin concentrations. No significant blood pressure changes occurred. Small increases in pulse rate and decreases in handwriting length occurred, but these changes were not associated with high fluphenazine levels.

Adult↗
PubMed1984

Within-individual variation in steady state plasma levels of different neuroleptics and prolactin.

Eleven male chronic schizophrenics were given, serially, oral pimozide, fluphenazine, and flupenthixol; the two latter were also given intramuscularly as decanoates in oil. Oral haloperidol was given before and after each drug. Analysis of variance of steady state plasma levels of the different neuroleptics showed considerable within-individual variation in such levels, probably due to differences in absorption and metabolism and between routes of administration. The findings suggest that if a patient fails to respond to one neuroleptic, there may be good pharmacokinetic reasons for switching him to another belonging to a different group, or for giving the same neuroleptic by a different route of administration. The study also showed that previous administration of one neurololeptic may influence the steady state level of another. The various neuroleptics produced different effects on plasma prolactin levels.

Administration, Oral↗
PubMed1983

Variation in oro-facial tardive dyskinesia during depot antipsychotic drug treatment.

Oro-facial (tardive) dyskinesia, occurring in patients on long-term antipsychotic (dopamine antagonist) medication, can be suppressed temporarily by increasing the drug dose. Lowering the dose can exacerbate the condition. In patients receiving regular fluphenazine decanoate (FPZ) and flupenthixol decanoate (FPT) injections, characteristic profiles of the fluctuations in plasma level concentrations, occurring during the injection interval, have been demonstrated. The possible effects of these relatively predictable plasma level changes on the severity of oro-facial dyskinesia, and parkinsonism, were investigated. Regular assessment of oro-facial dyskinesia throughout the injection interval was carried out in six patients receiving FPZ and two patients receiving FPT. In both groups, changes were observed in the severity of oro-facial dyskinesia consistent with the expected effects of drug level fluctuations. The main implication of this finding is that, in investigations of tardive dyskinesia in patients receiving depot medication, ratings should be carried out at a standard time relative to injections.

Aged↗
PubMed1980

Intermittent pimozide versus fluphenazine decanoate as maintenance therapy in chronic schizophrenia.

In a double-blind trial, 34 male chronic schizophrenic day-patients or in-patients in a hostel ward continued on fluphenazine decanoate given mostly once fortnightly or were switched to pimozide, given on four days each week. Over nine months relapse rates were similar for both groups, and while fewer patients on pimozide were prescribed antiparkinsonian drugs one quarter developed buccolingual masticatory dyskinesia. Plasma pimozide levels suggested satisfactory drug compliance. Average plasma prolactin levels were within the normal rage for untreated men in one quarter of non-relapsing patients on pimozide and three quarters on fluphenazine.

Chronic Disease↗
PubMed1979

Plasma fluphenazine levels by radioimmunoassay in schizophrenic patients treated with depot injections of fluphenazine decanoate.

1 Using a radioimmunoassay, plasma fluphenazine (FPZ) concentrations were examined in 33 schizophrenic patients during 38 intervals between injections of FPZ decanoate. Doses ranged from 12.5 to 150 mg and intervals from 1 to 5 weeks. At least three blood samples were taken between injections from each subject; also in 26 subjects additional samples were taken during the first 24 h post-injection. 2 FPZ was measurable in all plasma samples. 3 Each injection was followed by a rapid rise in plasma FPZ concentration to a maximum at 1-8 h. The height of this peak varied considerably. Within the next 12-36 h plasma FPZ fell to a level slightly above that found before injection and then remained stable until the next injection, thus confirming the steady release of FPZ from the depot over this period. 4 For the group, dose and mean plasma FPZ levels correlated strongly. 5 Despite this, there was a four-fold variation in plasma FPZ concentration among subjects receiving the same dose. 6 The FPZ level on the last day of an interval between injections was a satisfactory estimate of the mean FPZ level for the interval. 7 In one subject examined in this way, a positive correlation was found (r = 0.76) between plasma FPZ (by radioimmunoassay) and plasma prolactin levels.

Adult↗
PubMed1978

Sensitive gas-chromatographic determination of fluphenazine in human plasma.

We describe a method for quantitative determination of fluphenazine in human plasma, based on gas chromatography of its trimethylsilyl derivative and the use of a structurally similar internal standard. We determined its concentrations in plasma of four patients who were receiving the drug intramuscularly as its decanoate, in doses ranging from 12.5 to 250 mg; the concentrations in the plasma of these patients ranged from 0.25 to 11.8 microgram/liter. The precision (CV) of the method over the range 2 to 17 microgram/liter was 6.8% when fluphenazine was extracted from 5 ml of plasma. Of 18 other drugs tested, only thioridazine and the cis and trans forms of flupenthixol interfere with the determination.

Chromatography, Gas↗
PubMed1976

Clinical significance of plasma chlorpromazine levels. II. Plasma levels of the drug, some of its metabolites and prolactin in patients receiving long-term phenothiazine treatment.

Plasma levels of chlorpromazine (CPZ), 3 of its metabolites and prolactin were measured repeatedly in 18 chronic schizophrenic patients. The patients were studied while on chronic phenothiazine medication (chlorpromazine in 8, other phenothiazines in 10), during 4-6 weeks on placebo and during 6-12 weeks of CPZ treatment. The findings were compared with those obtained during acute CPZ treatment in patients who had received similar CPZ doses but no previous long-term phenothiazine medication. Plasma CPZ levels were similar in the chronic and the acute groups and so was their relation to dose. In neither group was therapeutic effect related to plasma CPZ level. In these chronic patients, in contrast to findings during acute CPZ treatment, neither prolactin level nor the appearance of parkinsonian symptoms was related to plasma drug level. In the chronic group both these effects were less pronounced during the period on CPZ which followed the placebo than were the corresponding effects during CPZ treatment in the acute group. Since plasma CPZ levels of the two groups were similar, these differences may be due to an acquired tolerance of the nervous system to some of the antidopaminergic effects of the drug.

Adult↗
PubMed1976

Clinical significance of plasma chlorpromazine levels. I. Plasma levels of the drug, some of its metabolites and prolactin during acute treatment.

Seventeen acute psychotic patients were studied in the course of chlorpromazine (CPZ) treatment. Blood samples were taken weekly both before and two hours after the morning CPZ dose. Plasma levels of CPZ, CPZ sulphoxide (CPZ SO) monodesmethylated CPZ (NOR1CPZ) and 7-hydroxy CPZ (7OH CPZ) were estimated by gas chromatography. Plasma prolactin, luteinizing hormone, testosterone and oestrogens were measured by radioimmunoassay. Six of the seven patients who showed no clinical improvement had plasma CPZ levels equal to or higher than those of patients who improved. 'Non-responders' has a greater proportion of CPZ SO in pre-dosage samples. The occurrence of parkinsonian side effects was associated with a mean plasma CPZ of greater than 50 ng/ml and a mean plasma prolactin of greater than 30 ng/ml two hours after dosage. The elevation of prolactin preceded the onset of parkinsonian symptoms by 1-2 weeks. There was a significant positive correlation between mean plasma prolactin and mean plasma CPZ levels. The prolactin response may prove a useful index of the central antidopaminergic effect of neuroleptic drugs.

Acute Disease↗
PubMed1975

Correlation between plasma levels of prolactin and chlorpromazine in psychiatric patients.

Plasma levels of chlorpromazine (CPZ) and prolactin were measured repeatedly in 14 psychiatric patients throughout CPZ treatment. Mean prolactin level was elevated in 11 subjects (all six women and five of eight men). Mean plasma prolactin correlated significantly with mean plasma CPZ but not with the dose of the drug. Only patients with mean plasma prolactin above 35 ng/ml developed Parkinsonian side-effects.

Administration, Oral↗