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Biomedical subjects

C H Koks

Publications and source records attributed to C H Koks.

30 records · Page 2Linked to original sources
PubMed1994

Application of a radioimmunoassay for determination of levels of zalcitabine (ddC) in human plasma, urine, and cerebrospinal fluid.

A specific and sensitive radioimmunoassay for the determination of levels of zalcitabine in human plasma, urine, and cerebrospinal fluid has been developed. Commercially available radiolabel and antiserum (Sigma Chemicals) were used after dilution in assay buffer. Prior to the immunoassay, standard and patient samples were subjected to solid-phase extraction on silica columns in order to obtain purified samples. The lower limit of quantitation was determined to be 1 ng/ml. Intra- and interassay variations were less than 11% for a number of quality control samples of drug in plasma and urine. Results from parallelism studies with plasma and urine demonstrated that samples outside the standard range (1 to 30 ng/ml) could be diluted by blank plasma or assay buffer, respectively. A large number of related compounds and potentially coadministered drugs were tested for cross-reactivity. Stability tests showed that heat treatment for 30 min at 60 degrees C or storage for 1 month at -30 degrees C did not affect zalcitabine concentrations in plasma or urine. The radioimmunoassay with solid-phase extraction for sample cleanup discussed here has been successfully applied in a pharmacokinetic study of a single patient, demonstrating its applicability for clinical pharmacokinetic research with zalcitabine.

Humans↗
PubMed1994

Pharmacokinetics of zidovudine and acetaminophen in a patient on chronic acetaminophen therapy.

OBJECTIVE: To report a case of a potential interaction between acetaminophen and zidovudine in a patient who had used high daily doses of acetaminophen over many years. CASE SUMMARY: A 43-year-old man presented with HIV-1 infection, recurrent oral candidiasis, and chronic use of acetaminophen, codeine, and diazepam before he started zidovudine therapy. Although literature was available regarding short-term combined use of acetaminophen and zidovudine, information was lacking on zidovudine therapy and kinetics after long-term use of acetaminophen. Acetaminophen and zidovudine pharmacokinetics were determined on several occasions. The results showed extremely rapid absorption of both drugs (tmax the time to reach maximum concentration, 10-15 minutes for acetaminophen and 15-20 minutes for zidovudine) and, consequently, relatively high maximum plasma concentration (Cmax). No influence on other pharmacokinetic parameters of either drug could be detected. Because the effect of high Cmax values of zidovudine is unknown, the patient was treated with a third of the dose of zidovudine used at that time (zidovudine 100 mg q6h). No toxicity or opportunistic infections developed within the next 8 months, after which the patient died of a cause unrelated to HIV infection. DISCUSSION: The observed pharmacokinetic profiles of both drugs are discussed and compared with two studies dealing with zidovudine therapy in combination with short-term use of acetaminophen and with a case report of acetaminophen-induced hepatotoxicity during concomitant use of zidovudine. CONCLUSIONS: Long-term use of acetaminophen may accelerate the absorption of zidovudine. Although other causes cannot be ruled out, there was no influence on other pharmacokinetic parameters of zidovudine. No influence of zidovudine on acetaminophen concentrations was found. Combined use of zidovudine 100 mg q6h and acetaminophen 500 mg q4h appeared to be safe and effective for at least eight months.

Acetaminophen↗
PubMed1993

Ocular complications of the acquired immunodeficiency syndrome. Focus on the treatment of cytomegalovirus retinitis with ganciclovir and foscarnet.

The most common ocular complication in patients with the acquired immunodeficiency syndrome (AIDS) is cytomegalovirus retinitis. Incidence figures vary from 20 to 76%. Patients with cytomegalovirus may suffer from mild visual impairment of one or both eyes, but as the disease progresses the retinitis will almost certainly lead to blindness. Although cytomegalovirus retinitis is not a life-threatening infection, it can largely diminish the patient's quality of life. Clinical trials for the treatment of cytomegalovirus retinitis with a number of antiviral drugs have resulted in two drugs of choice, ganciclovir and foscarnet. Both drugs have an initial efficacy with induction therapy of 80-90%, but maintenance therapy is always needed to prevent a relapse. To exclude systemic side-effects of ganciclovir, intravitreal administration has been investigated with good results. Combination therapy of foscarnet and ganciclovir may be worthwhile in resistant cytomegalovirus retinitis.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Penetration of zidovudine into the cerebrospinal fluid of patients infected with HIV.

OBJECTIVE: To investigate penetration of zidovudine (ZDV) into the cerebrospinal fluid (CSF) of HIV-infected patients for whom a lumbar puncture was indicated. DESIGN: A prospective study. SETTING: General 525-bed hospital with special funding for treatment and research of HIV-infected patients. PATIENTS, PARTICIPANTS: Thirty-nine patients with a medical indication for lumbar puncture who used ZDV chronically were included in this study (50 samples in total). MAIN OUTCOME MEASURE: Determination of ZDV and proteins in CSF and plasma samples. RESULTS: CSF concentrations of ZDV showed little fluctuation 1-8 h after the last ingestion of ZDV. In contrast, plasma levels displayed large variability in this period and decreased exponentially over time. As a result, the CSF/plasma ratio increased linearly over time. No significant relation between the ZDV dose, neither the medical indication for lumbar puncture nor the protein ratio (as a measure for the integrity of the blood-brain barrier), and CSF levels of ZDV was found. The CSF/plasma ratio of ZDV did not give essential information on drug distribution into CSF. CONCLUSIONS: Penetration of ZDV into the CSF appears to be independent of the dose (range, 200-1250 mg daily), which may be an explanation for the efficacy of low doses of ZDV in the prevention and treatment of HIV-related neurological diseases. ZDV levels were at steady-state during the first 6 h after ingestion. The CSF/plasma ratio of ZDV concentrations is not an appropriate marker for drug penetration into CSF.

Adult↗
PubMed1993

Pharmacokinetic interaction between rifampin and zidovudine.

A potential pharmacokinetic interaction between rifampin (Rimactan, Rifadin) and zidovudine (AZT, Retrovir) was investigated in the population of human immunodeficiency virus-infected patients at our hospital. The results from four patients who were on long-term (> or = 6 months) combination therapy with zidovudine and rifampin are presented. In all cases of combined use of zidovudine and rifampin, a lower area under the plasma concentration-time curve (AUC) and, consequently, a higher apparent clearance of zidovudine were found, compared with a reference population of zidovudine users. Patients had a low to normal maximum concentration of zidovudine in plasma. Elimination half-lives were normal in all but one patient. Zidovudine glucuronide concentrations were determined in three patients and three control subjects. The patients all had relatively higher peak plasma concentrations and higher AUCs of zidovudine glucuronide than the control subjects. In one patient, zidovudine and zidovudine glucuronide were also measured 2.5 months after discontinuation of rifampin. The AUC of zidovudine increased by a factor of 2. These data are in agreement with an enzyme-inducing effect of rifampin on the glucuronidation of zidovudine. They indicate that long-term combination therapy of rifampin and zidovudine leads to increased clearance of zidovudine, which may have therapeutic consequences.

Adult↗
PubMed1992

Didanosine, a new antiretroviral drug. A review.

In this article the literature about didanosine, an antiretroviral drug, is reviewed. The mechanism of action, biochemical pharmacology, pharmacokinetics, and clinical results of phase-I trials are discussed. Serious adverse effects such as pancreatitis and peripheral neuropathy have occurred in these trials. An antiretroviral effect was observed in terms of an increase in CD4+ lymphocytes and a decrease in p24 antigen levels in HIV-infected individuals. Didanosine seems to be a promising drug against HIV infection, but knowledge about its clinical efficacy is scanty.

Animals↗
PubMed1990

A simple high pressure liquid chromatographic method for the determination of fluorouracil to monitor patients on regional infusion for hepatic metastases.

A rapid and sensitive high pressure liquid chromatographic method has been developed for the routine monitoring in serum of the antineoplastic agent fluorouracil, during continuous intraportal administration. Serum spiked with internal standard, bromouracil, was gently shaken for 10 min with ethylacetate at an acidic pH. The evaporated extract was dissolved in the mobile phase containing potassium phosphate buffer. Assays were performed at ambient temperature on a Chrompack LiChrosorb RP 18 column (2 X 100 X 3.0 mm) equipped with a guard column. The retention time of fluorouracil was 2-6 min. The calibration curve was linear from 25 to 2,000 ng/ml. The coefficient of variation was less than or equal to 1.6% for within-run precision and less than or equal to 2.9% for day-to-day precision. The mean recovery of fluorouracil was 57%.

Chromatography, High Pressure Liquid↗
PubMed1988

Regional infusion of fluoropyrimidines for hepatic metastases of colorectal cancer.

Recent reports on regional chemotherapy for hepatic metastases of colorectal origin are reviewed. Because of reported side effects and lack of evidence for its superiority over conventional intravenous administration, intra-arterial administration of fluoropyrimidines cannot be advised for routine use, but should be restricted to centres participating in clinical trials on this subject.

Clinical Trials as Topic↗