Preliminary Experience with Combined Therapy using Rifampicin and Isoprodian (L73A)

Freerksen, E

doi:10.5935/0305-7518.19750059

Cited by 3 publications

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“…In conformity with L eiker and K amp [47], O promolla and T onello [51], Rees et al [65], Shepard et al [78][79][80], our investigations have demonstrated [20,22,23,25,32,69,70] that rifampicin (RMP) is the most effective substance.…”

Section: Selection Of the Medicamentsmentioning

confidence: 97%

“…The main factors by which our strategy is determined have been dis cussed elsewhere [20,23,25,26,32], This presentation reviews only a few aspects which are of special relevance to an eradication programme.…”

Section: Discussion and Comments To Our Proceduresmentioning

confidence: 99%

“…Up to the present time, these high requirements are satisfied only by determinations of serum activity in healthy volunteers (or patients) [20,23,25,33,70,71,73]. Also this method is only applicable when the micro organism is available in vitro.…”

Section: Drugs and Their Evaluationmentioning

confidence: 99%

“…The goal can, therefore, only be reached by applying a highly effective chemo therapy [18,20,22,25] which (a) rapidly renders the patient non-infectious (and thus stops dissemination of living bacilli), and (b) definitely cures the patient of his leprosy in a reasonably short time.…”

Section: General Aspectsmentioning

confidence: 99%

“…M. marinum can be easily cultivated, it is pathogenic to man, a mycobacterial species with little chemosensitivity, and the mouse can be used as a laboratory animal in serial testings. At least some of the limitations in leprosy therapy research were thus re moved; the specific leprosy therapy changed into a universal antimycobacterial therapy [18,22,23,25,28,29].…”

Section: Drugs and Their Evaluationmentioning

confidence: 99%

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Leprosy Eradication Project of Malta

Freerksen¹,

Rosenfeld²

1977

Chemotherapy

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This is the first publication of the initial 5-year-period of the eradication programme since its introduction in the Maltese Islands in the second half of 1972. All patients were treated with a combined drug regimen, its chief components being rifampicin (RMP), prothionamide (PTH), isoniazid (INH) and diaminodiphenyl-sulfone (DDS). To simplify the therapeutic technique, PTH, INH and DDS were given as a fixed combination. Other medications, such as DDS-free regimens, were whenever possible also given as fixed combinations. Fixed combinations not only make treatment simpler, but also guarantee a more reliable acceptance of the medication and the adherence to the dosage proportions which play an important role with regard to the effectiveness. For an eradication programme the classification into the different leprosy types plays not a too important role. It was rather our goal to cure each single patient so as to eliminate him as a possible source of infection. Whether or not this goal has been reached was as far as possible related to the results of the bacteriological assessment. Of the originally recorded 210 patients 206 were included in the first part of the programme (groups I–III). By the end of 5 years, a total of 20 patients had left the programme (death or emigration) so that 186 patients remained registered per June, 1977. In 180 cases treatment has been discontinued; 6 patients are still under therapy. The relapse-free observation periods are more than 2 years in 160 patients, more than 3 years in 120 patients, and more than 4 years in 12 patients. 31 patients joined the programme when it was already under way, namely 11 patients in 1973, 9 patients in 1974, 6 patients in 1975, and 5 patients in 1976. These newly registered cases were grouped separately (group IV). 27 patients were found to be bacteriologically positive; 10 of them are meanwhile negative, 11 are still being treated. Under observation without therapy are 19. One patient died of nonspecific disease in 1976. In continuation of the programme we are aiming at (a) conclusive treatment of the rest of the patients who are still under therapy, (b) conclusive treatment of the patients according to group IV, (c) regular observation of all cases for the absence of relapses, and (d) search for new cases and inclusion of such eventually newly identified cases in the programme. Further scientific evaluation of the material, chiefly in the bacteriological, clinical, pathological and genetic field, will require lengthy investigations which we are working at. A larger quantity of well-examined and well-classified material has accumulated since the start of the programme. The material is at the disposal also of all colleagues outside Borstel Institute. Up to the present, we have collected approximately 30,000 histological slides, representing all stages of leprosy, i.e. from the period before, during and after treatment (about 5000 biopsies). The article explains the prerequisites for an eradication programme which in principle can serve as a model for si...

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Section: Selection Of the Medicamentsmentioning

confidence: 97%

Section: Discussion and Comments To Our Proceduresmentioning

confidence: 99%

Section: Drugs and Their Evaluationmentioning

confidence: 99%

Section: General Aspectsmentioning

confidence: 99%

Section: Drugs and Their Evaluationmentioning

confidence: 99%

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Leprosy Eradication Project of Malta

Freerksen¹,

Rosenfeld²

1977

Chemotherapy

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Combined Therapy in Leprosy

Freerksen¹,

Rosenfeld²,

Bonnici³

et al. 1978

Chemotherapy

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This report is based on data obtained from 64 lepromatous cases. Despite many years of DDS monotherapy, the homogenates from biopsies of these patients revealed 10⁴ or more bacteria. From the beginning of combination therapy with synergisticacting substances (rifampicin + isoprodian (INH + PTH + DDS) the logarithms of the number of bacteria in the homogenates decreased, both during treatment period and during treatment-free observation period (Figs. 3–8). During the whole time biopsies were taken almost monthly. A considerable regression of the bacterial mass or even «negativity» could be observed within a relatively short time. Once started, the process of reduction of bacteria continued also after termination of therapy. To be able to evaluate a medication, therapy-free observation periods (for a minimum of 5 years) are indispensable.

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Clinical Pharmacokinetic Considerations in the Treatment of Patients with Leprosy

Venkatesan

1989

Clinical Pharmacokinetics

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On the basis of the efficacy of the available agents, the World Health Organization has recommended only 4 drugs for combined chemotherapy of leprosy: rifampicin, dapsone, clofazimine and ethionamide/prothionamide. Thiacetazone and isoniazid are also used to a lesser extent by some physicians. Pyrazinamide may find a place in treating 'persister' bacilli. Dapsone is absorbed slowly after oral administration. Peak plasma drug concentration is reached at about 4 hours; absorption half-life is 1.1 hours; elimination half-life is about 30 hours. Oral availability is around 90%. Dapsone is approximately 70% protein-bound, while its monoacetylated metabolite is almost entirely bound. Dapsone crosses the placenta and is excreted into breast milk. It is metabolised via acetylation and N-hydroxylation, but acetylation polymorphism has no effect on dapsone handling by leprosy patients. Dapsone penetrates into sciatic nerves of experimental animals but its presence has not been demonstrated in Schwann cells. Oral doses of rifampicin are rapidly and completely absorbed. The bioavailability is greater when the drug is given before meals; peak concentrations occur at 1 to 2 hours. 80 to 90% of rifampicin is bound to plasma proteins, and the drug is found in saliva, cerebrospinal fluid and breast milk. Its main metabolite, desacetyl rifampicin, also exhibits antimycobacterial activity in tuberculosis. Rifampicin induces its own metabolism, as well as that of dapsone and steroids. Absorption of dapsone and rifampicin is reported to be reduced in leprosy patients. Clofazimine has been in use in leprosy treatment since 1960. In higher doses it exerts an anti-inflammatory action which is useful in treating leprosy patients in reaction. Oral absorption of the drug is slow and dose-dependent; faecal excretion also increases with dose. Single- and multiple-dose studies have shown a plasma half-life of around 10 days. Bioavailability of the drug is higher when given with food than when fasting; the peak plasma concentration occurs at 4 to 8 hours when the drug is administered with breakfast. After absorption, the drug is thought to circulate in protein-bound form, accounting for the fact that it is deposited in various tissues. Uneven distribution and prolonged retention in the tissues are special features of clofazimine metabolism. One unconjugated and 2 conjugated metabolites have been detected in urine, and the urinary excretion of both the parent compound and its metabolites is around 1% of the dose.(ABSTRACT TRUNCATED AT 400 WORDS)

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Preliminary Experience with Combined Therapy using Rifampicin and Isoprodian (L73A)

Cited by 3 publications

References 0 publications

Leprosy Eradication Project of Malta

Leprosy Eradication Project of Malta

Combined Therapy in Leprosy

Clinical Pharmacokinetic Considerations in the Treatment of Patients with Leprosy

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