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Biomedical subjects

T K Daneshmend

Publications and source records attributed to T K Daneshmend.

At least 37 records · Page 2Linked to original sources
PubMed1988

Devastating diarrhoea caused by azathioprine: management difficulty in inflammatory bowel disease.

Azathioprine toxicity complicated the management of four patients with inflammatory bowel disease. All patients received the drug as adjunctive therapy to steroids when responses to the latter were poor. After a variable sensitising period the patients developed severe diarrhoea and abdominal pain and this was believed at first to be a manifestation of their underlying diseases but rechallenge with azathioprine reproduced the problem. During three episodes described emergency admission to hospital and resuscitation with intravenous fluids was required. The cases illustrate the difficulty clinicians have in recognising drug induced effects which mimic the underlying disease. When a patient suspects a reaction to azathioprine we believe any rechallenge should only be undertaken in the controlled hospital environment.

Adolescent↗
PubMed1988

Clinical pharmacokinetics of ketoconazole.

Ketoconazole, a synthetic imidazole antifungal, is effective for superficial fungal infections, genital candidosis and chronic mucocutaneous candidosis, and has been used in immunocompromised patients and advanced prostatic carcinoma. Absorption of ketoconazole is variable after oral administration, with large variability in peak serum concentrations. Antacids reduce, and food or dilute hydrochloric acid increase, absorption. Renal failure and bone marrow transplantation are associated with reduced absorption. Ketoconazole is not absorbed systemically after topical administration, and minimally absorbed from the vagina. Distribution of ketoconazole varies according to the tissue sampled, the underlying disease and the dose and duration of treatment. Ketoconazole does not cross the intact blood-brain barrier, and crosses to only a limited extent in fungal meningitis. Urinary concentrations of ketoconazole are usually low, but vaginal and vaginal tissue concentrations correlate with those in serum. Seminal fluid concentrations are inadequate for treatment of epididymitis. Ketoconazole is 83.7% plasma protein (mainly albumin) bound, and 15.3% is erythrocyte bound, resulting in only 1% of free drug. Animal studies indicate strong binding to the cytochrome P-450 mono-oxygenase complex. Extensive metabolism to inactive metabolites occurs, the products being mainly excreted in the faeces. Saturable hepatic first-pass metabolism is probable. The half-life of ketoconazole is dose-dependent, increases during long term treatment, suggesting auto-inhibition of metabolism. The kinetics after oral administration fit a 2-compartment model. Drug interactions of theoretical, if not practical, significance include warfarin, chlordiazepoxide, methylprednisolone, cyclosporin and drugs known to induce microsomal enzymes. In each case, some dosage adjustment for ketoconazole, or the interacting drug, may be required.

Administration, Intravaginal↗
PubMed1987

Oxamniquine pharmacokinetics in hepatosplenic schistosomiasis in the Sudan.

Oxamniquine pharmacokinetics were determined in five normal Sudanese subjects and nine Sudanese patients with advanced hepatosplenic schistosomiasis, given 1 g as a single oral dose. There were no significant differences in oxamniquine mean area under the plasma concentration time curve (AUC), plasma half life (T1/2), or time to reach peak concentration (Tmax). However, patients had a 19% lower mean AUC, a 36% higher T1/2, and a 23% increase in Tmax. The peak concentration (Cmax) was 36% lower in patients (P = 0.04). There was no correlation between disease severity and oxamniquine pharmacokinetic values. A significant correlation between oxamniquine AUC and T1/2 suggests that its elimination may be non-linear. The higher dosage requirements for oxamniquine in the Sudan are unlikely to be due to lower plasma concentrations amongst the Sudanese.

Adult↗
PubMed1986

Ketoconazole pharmacokinetics during chronic dosing in adults with haematological malignancy.

Ketoconazole pharmacokinetics were determined in nine adults with haematological malignancy after one week on a 200 mg daily dose and later after one week on a 400 mg daily dose. The area under the serum concentration time curve (AUC) reached 12.3 +/- 7.7 mg/l.h (mean +/- S.D.) on the 200 mg dose and increased to 23.0 +/- 18.2 mg/l.h on the 400 mg dose (p less than 0.05). The half-life of ketoconazole was 3.1 +/- 1.9 h on the 200 mg dose and 3.5 +/- 1.7 h on the 400 mg dose. Peak concentrations were 3.2 +/- 1.8 mg/l and 4.6 +/- 3.2 mg/l on the 200 mg and 400 mg doses, respectively. Trough ketoconazole concentrations were undetectable 24 h after either dose. There was no correlation between the leucocyte count and any pharmacokinetic parameter for ketoconazole. Variation in AUC was 20-fold on the 200 mg daily dose and 8-fold on the 400 mg per day regimen. Measurement of serum levels during ketoconazole treatment appears necessary in view of the unpredictable concentrations achieved. Once-a-day dosage regimens of ketoconazole in immunocompromised patients may be inappropriate. Future clinical trials should adopt a two or three times a day dosing regimen, as this may confer a pharmacokinetic and therapeutic advantage.

Adult↗
PubMed1986

Metronidazole metabolism following oral benzoylmetronidazole suspension in children with giardiasis.

A suspension of benzoylmetronidazole (6.4% w/v) was given orally at a dose of 15-25 ml, equivalent to 0.6-1 g metronidazole, once a day for three days to 11 children with giardiasis. Blood samples were collected after the first and third doses for analysis of plasma metronidazole and its main oxidative metabolite by high performance liquid chromatography. Peak metronidazole concentrations were 22.60 +/- 8.52 mg/l (mean +/- S.D.) after the first dose, and 30.22 +/- 10.06 mg/l after the third dose, occurring at 3.6 +/- 1.4 and 4.4 +/- 2.9 hours post-dose, respectively. Peak concentrations of the metabolite were 4.26 +/- 1.94 mg/l after the first dose and 7.96 +/- 3.63 mg/l after the third dose, occurring 7.2 +/- 1.6 and 9.1 +/- 3.3 h post-dose, respectively. Calculation of plasma metronidazole half-life and clearance values was not possible. This study shows that oral administration of metronidazole as its benzoyl ester slows the rate of metronidazole absorption, followed by sustained plasma concentrations and a prolonged elimination phase. Giardiasis does not appear to prevent metronidazole absorption. Concurrent giardiasis is unlikely to influence metronidazole therapy for systemic anaerobic infections.

Administration, Oral↗
PubMed1986

Systemic absorption of miconazole from the vagina.

The serum concentrations of miconazole were measured in 11 healthy adult females for 72 hours following a single 1200 mg vaginal pessary. The mean peak serum miconazole concentration was 10.4 micrograms/l and the mean elimination half life was 56.8 h. The mean area under the serum concentration time curve was 967 micrograms/l.h. The calculated mean systemic bioavailability of the vaginal pessary was 1.4%. There was large intersubject variation in serum miconazole pharmacokinetics. This formulation may provide effective single dose treatment for vaginal candidosis.

Absorption↗
PubMed1986

Assessment of oxidative metabolism in adults with hepatocellular carcinoma in the Sudan.

The hypothesis that an increased rate of oxidative metabolism may be an initiator or promoter of hepatocellular carcinoma was tested in vivo. Elimination of antipyrine (phenazone) was used as an index of the activity of microsomal mixed function oxidative enzymes. Plasma antipyrine kinetics were examined in 10 patients with hepatocellular carcinoma and in 10 normal Sudanese adults. The half life, volume of distribution and clearance of antipyrine in patients were 18.8 +/- 7.9 hours (mean +/- SD), 33.8 +/- 7.7 litres and 23.7 +/- 10.1 ml/min, respectively; and in normal adults were 20.3 +/- 8.8 hours, 40.1 +/- 10.4 litres and 25.7 +/- 12.0 ml/min, respectively. These differences were not significant. Antipyrine plasma clearance when corrected for weight was similar in the two groups. This study suggests that in a population at risk for hepatocellular carcinoma, the overall activity of mixed function oxidative enzymes is not an important determinant in selectively increasing this risk.

Adult↗
PubMed1984

Systemic absorption of ketoconazole from vaginal pessaries.

Eight healthy female subjects were each given (a) ketoconazole 400 mg orally, (b) ketoconazole 400 mg as a single vaginal pessary, (c) ketoconazole 800 mg as two vaginal pessaries, and (d) ketoconazole 1200 mg as three vaginal pessaries. The area under the plasma concentration time curve (AUC) after the oral dose was 51.41 +/- 10.99 mg l-1 h (mean +/- s.d.) and the half-life of ketoconazole was 2.98 +/- 1.41 h. The AUCs after vaginal administration were 0.27 +/- 0.14, 0.52 +/- 0.25, and 0.43 +/- 0.22 mg-1 l h following the 400, 800 and 1200 mg pessaries respectively. Systemic absorption of single doses of vaginally administered ketoconazole appears to be negligible in the absence of vaginal infection. There were no local or systemic side effects related to ketoconazole in these healthy volunteers.

Absorption↗