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Biomedical subjects

C Y Chiang

Publications and source records attributed to C Y Chiang.

At least 37 records · Page 2Linked to original sources
PubMed1998

Tuberculous empyema.

The clinical courses of 35 tuberculous empyema patients were investigated retrospectively from November 1990 through November 1995. Most patients had nonspecific symptoms and signs but with far-advanced pulmonary parenchymal lesions in their chest roentgenographs. The effusions showed neutrophilic leukocytosis with a 60% positive culture rate for Mycobacterium tuberculosis. Multidrug resistant strains were found in 7 out of 18 cultures. All patients received chemotherapy and eight of them underwent additional surgical management. Twenty-two (62.9%) patients had been treated successfully and one patient is still under treatment. The remaining 12 patients either died during treatment or defaulted; and four (11.4%) of them had died of tuberculosis. We conclude that the treatment outcome of tuberculous empyema is less satisfactory than that of pulmonary tuberculosis, however, modern multidrug chemotherapy with repeated drainage and opportune surgical interventions could be in prospect of successful treatment of tuberculous empyema.

Adolescent↗
PubMed1998

NMDA receptor mechanisms contribute to neuroplasticity induced in caudalis nociceptive neurons by tooth pulp stimulation.

We recently demonstrated that application of mustard oil (MO), a small-fiber excitant and inflammatory irritant, to the rat maxillary molar tooth pulp induces significant and prolonged increases in jaw muscle electromyographic (EMG) activity that are suggestive of central neuroplasticity. Because small-fiber afferents, including pulp afferents, access nociceptive neurons in trigeminal (V) subnucleus caudalis, this study examined whether pulpal application of MO induces neuroplastic changes in caudalis nociceptive neurons (wide dynamic range and nociceptive specific) and whether central N-methyl--aspartate (NMDA) receptor mechanisms are involved in these MO-induced neuroplastic changes. After pretreatment with vehicle (saline, 10 microliter i.t.) to the surface of the medulla, the pulpal application of MO to the maxillary molar tooth pulp produced a significant increase in neuronal spontaneous activity, a significant expansion of the pinch and/or tactile mechanoreceptive field (RF), a significant decrease in mechanical threshold, and significant increases in neuronal responses to graded pinch stimuli. Compared with vehicle-treated rats, pretreatment with the NMDA receptor antagonist MK-801 (10 microgram/10 microliter i.t.) followed by MO application to the pulp in another group of rats significantly reduced or abolished these MO-induced neuroplastic changes in nociceptive neurons. In another group of rats pretreated with saline (intrathecally), mineral oil application to the pulp did not show any significant changes in spontaneous activity or RF properties over the 40-min observation period. The pulpal application of MO in other rats (pretreated with saline, intrathecally) did not produce any significant neuroplastic changes in caudalis low-threshold mechanoreceptive neurons. These results indicate that the MO-induced activation of molar pulpal afferents can produce profound NMDA receptor-related neuroplastic changes in caudalis nociceptive neurons. Such neuroplastic changes may contribute to the hyperalgesia and spread of pain that can be associated with pulpal inflammation.

Animals↗
PubMed1998

Screening of human immunodeficiency virus infection in pulmonary tuberculosis patients in Taiwan.

To disclose the impact of human immunodeficiency virus (HIV) infection on the tuberculosis epidemic in Taiwan, we prospectively screened for HIV infection in patients with active pulmonary tuberculosis. A total of 378 patients who were admitted to the Taiwan Provincial Chronic Disease Control Bureau from January through December 1996 were enrolled. HIV serologic testing was performed by enzyme-linked immunosorbent assay (ELISA). A positive ELISA test was confirmed by Western blot analysis. One patient was infected with HIV. We conclude that the impact of HIV infection on the epidemic of tuberculosis in Taiwan is not significant at present.

Adolescent↗
PubMed1998

Short-course chemotherapy for isoniazid-resistant pulmonary tuberculosis.

Standard short-course chemotherapy including isoniazid, rifampicin, pyrazinamide, and ethambutol has been the recommended treatment for tuberculosis in Taiwan since November 1990. The effectiveness of this treatment was evaluated retrospectively in 108 patients with isolates resistant to isoniazid alone and 115 patients with drug-susceptible pulmonary tuberculosis diagnosed and treated at the Taiwan Provincial Chronic Disease Control Bureau from November 1990 through December 1995. The success rate of treatment was 94.4% in patients with isoniazid-resistant Mycobacterium tuberculosis strains, which was not significantly different from the 97.4% rate in patients with susceptible strains. Of the patients treated successfully, no bacteriologic relapse was found in 97 patients with isoniazid-resistant strains or 103 patients with drug-susceptible strains 12 months after the end of chemotherapy. No significant advantage in treatment outcome was found in patients infected with isoniazid-resistant strains who received chemotherapy for more than 6 months (successful treatment rate, 95.0% vs 92.8%), but the failure rate was higher in patients with a previous history of antituberculosis therapy (17.6% vs 3.3%). We conclude that short-course chemotherapy is effective for isoniazid-resistant pulmonary tuberculosis and that there is no significant difference in treatment outcome between patients with or without isoniazid-resistant disease.

Antitubercular Agents↗
PubMed1997

NMDA receptor involvement in neuroplastic changes induced by neonatal capsaicin treatment in trigeminal nociceptive neurons.

NMDA receptor involvement in neuroplastic changes induced by neonatal capsaicin treatment in trigeminal nociceptive neurons. J. Neurophysiol. 78: 2799-2803, 1997. This study examines whether 1) the neonatal loss of C-fiber afferents results in neuroplastic changes in the mechanoreceptive field (RF) properties and spontaneous activity of nociceptive neurons in trigeminal subnucleus caudalis (medullary dorsal horn) of adult rats, and that 2) N-methyl--aspartic acid (NMDA) receptor mechanisms are involved in these neuroplastic changes. Compared with vehicle-treated (i.e., control, CON) rats, capsaicin-treated (CAP) rats showed a marked increase in neuronal spontaneous activity and RF size per se, but these neuroplastic changes could be significantly reduced by MK-801 (1 mg/kg, iv), a noncompetitive NMDA receptor antagonist; RF size and spontaneous activity remained unchanged in CON rats after MK-801 administration and in CAP rats after vehicle (saline, iv). Administration of 7-chlorokynurenic acid intrathecally (5 microgram/10 microliter), an antagonist of strychnine-insensitive glycine bindin sites on the NMDA receptor, also significantly reduced neuronal RF size and spontaneous activity in CAP rats, but not in CON rats. These data provide evidence that C-fiber afferents play a role in shaping the properties of nociceptive neurons and that the neuroplastic changes involve NMDA receptor mechanisms.

Animals↗
PubMed1997

Initial drug resistance of Mycobacterium tuberculosis in Taiwan.

The prevalence and mortality rate of pulmonary tuberculosis in adults are high in Taiwan. Because the emergence of drug-resistant tuberculosis is one of the major causes of this sustained high tuberculosis mortality, surveillance of initial drug resistance is important. We tested Mycobacterium tuberculosis isolates from 1,935 newly diagnosed tuberculosis patients from January 1990 through December 1995 at the Taiwan Provincial Chronic Disease Control Bureau. The overall initial drug resistance rate was 12.3%; 8.7% of isolates were resistant to only one drug, 2.6% to two drugs, 0.7% to three drugs, and 0.3% to four drugs. The resistance rates to individual drugs were: streptomycin, 5.7%; isoniazid, 9.2%; ethambutol, 0.7%; and rifampin, 1.5%. The frequency of multidrug-resistant M. tuberculosis (resistant to at least isoniazid and rifampin) was 1.2%. In view of the high initial isoniazid resistance rate and low initial ethambutol resistance rate, ethambutol should be added to the regimen for the initial treatment of tuberculosis in Taiwan. The emergence of multidrug-resistant M. tuberculosis is ominous and should be considered when treating patients in Taiwan.

Adolescent↗
PubMed1996

Treatment of multidrug-resistant tuberculosis in Taiwan.

Eighty-seven patients with multidrug-resistant tuberculosis (MDR-TB) diagnosed between 1988 and 1990 were treated with isoniazid and at least three other effective second-line drugs based on in vitro susceptibility tests. Of these patients, 10% failed to adhere to the regimen and 43% remained sputum positive after 6 months of treatment. Only 47% showed sputum conversion within 6 months of treatment and 12% of them relapsed during the first year of follow-up. From September 1987 to July 1989, 36 patients with MDR-TB were treated with a regimen containing rifabutin, isoniazid and at least three other susceptible drugs. Only 47% achieved a sustained sputum conversion. Four died during treatment due to disease progression. From March 1992 to July 1993, 17 cases of MDR-TB were treated with an ofloxacin-containing anti-TB regimen for 12-24 months. Two failed to adhere to the regimen for more than 1 month during the first 6 months of therapy. Among the remaining 15, 26% failed to achieve sputum conversion, 73% achieved bacterial conversion, 9 within 1 month and the other 2 within 2 months. No significant adverse effect was associated with ofloxacin use. We concluded that ofloxacin is a better choice among the more toxic and less potent second-line drugs, and should be used along with other anti-TB drugs in treating patients with MDR-TB.

Adult↗
PubMed1995

Recurrent hypertensive intracerebral hemorrhage.

Hypertensive intracerebral hemorrhage has been considered as a one-time event with rare recurrence. This observation is quite different from our experience in Taiwan. We, therefore, conducted a systematic review of our series of consecutive patients with recurrent bleeding. During a 2-year period, we encountered 47 patients with recurrent hypertensive intracerebral hemorrhage from a total of 892 consecutive patients with hypertensive hemorrhage (5.3%). There were 25 men and 22 women with a mean age of 59 +/- 10 (range: 36-78) years at the onset of the first hemorrhage and 62 +/- 9 (range: 39-80) years at the second hemorrhage. The median interval between 2 hemorrhages was 2 years and 4 months (range: 1 month to 8.5 years). All except one recurrent hemorrhages occurred at a site different from the previous one. Of the 38 patients admitted to our hospital for both hemorrhages only 5 were regularly treated with antihypertensive therapy. The outcome for the recurrent bleeding was grave: 26% died and 51% became totally dependent or vegetative. Recurrent hypertensive hemorrhage is not as rare as previously thought; it comprises 5.3% of our patients with hypertensive intracerebral hemorrhage. The recurrent hemorrhage, however, rarely occurs at the same location as the previous one. Uncontrolled hypertension appears to be an important risk factor for the recurrence. Control of blood pressure after the first bleeding should be attempted to prevent recurrent hemorrhage.

Adult↗
PubMed1994

Parabrachial area and nucleus raphe magnus-induced modulation of nociceptive and nonnociceptive trigeminal subnucleus caudalis neurons activated by cutaneous or deep inputs.

1. The aim of this study was to test whether parabrachial area (PBA) stimulation exerts inhibitory influences on the spontaneous activity and responses evoked by skin and deep afferent inputs in trigeminal subnucleus caudalis (Vc) neurons, and to compare these effects with those of nucleus raphe magnus (NRM) stimulation. A total of 92 nonnociceptive and nociceptive Vc neurons was recorded in urethan/alpha-chloralose-anesthetized rats. Each neuron was functionally classified as low-threshold mechanoceptive (LTM), wide dynamic range (WDR), nociceptive-specific (NS), nociceptive convergent with both skin and deep inputs (S+D), or deep nociceptive (D); the LTM neurons could be subdivided as rapidly adapting (RA) or slowly adapting (SA). Conditioning stimulation was applied to histologically verified sites in PBA and NRM. 2. The spontaneous or evoked activity of all classes of neurons could be inhibited by PBA as well as by NRM stimulation, but generally the incidence and magnitude of inhibition were lower for the LTM neurons. Occasionally, facilitation of neuronal activity was also produced by PBA and NRM stimulation. 3. The spontaneous activity of 11 LTM neurons (6 RA, 5 SA), 13 nociceptive neurons (6 WDR, 7 NS), and 5 D neurons was tested with stimulation of PBA or NRM or both. LTM spontaneous activity was more significantly inhibited by NRM stimulation than by PBA stimulation, whereas both NRM and PBA stimulation had similar and significant inhibitory effects on NS, WDR, and D neurons. 4. The evoked nonnociceptive responses of 28 LTM neurons (16 RA, 12 SA) and of 6 WDR neurons were also tested with stimulation of PBA or NRM or both. The magnitudes of inhibition of the responses produced by PBA conditioning stimulation were statistically significantly less than those induced by NRM conditioning stimulation. 5. The cutaneous and deep nociceptive responses of cutaneous nociceptive neurons (9 NS, 19 WDR) and seven D neurons, respectively, were also tested with PBA and NRM stimulation. There was a significant difference in potency between PBA- and NRM-induced inhibition, but no difference in the magnitude of inhibitory effects among NS, WDR, and D neurons. For both PBA and NRM conditioning stimulation, graded increases in intensities of stimulation produced linear increases in inhibitory effects on nociceptive responses; an increase in stimulation frequency from 5 to 400 Hz also produced increases in inhibition of the nociceptive responses. 6. In five S+D nociceptive convergent neurons, the responses elicited by deep inputs were more powerfully inhibited by PBA stimulation than those elicited by cutaneous inputs.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗
PubMed1993

Responses of neurons in the rat thalamic nucleus submedius to cutaneous, muscle and visceral nociceptive stimuli.

The findings of recent studies have suggested that nucleus submedius (Sm) may be an important thalamic relay for nociceptive information. The aim of the present electrophysiological study was to examine in greater detail the activity and response properties of neurons in the rat Sm in order to further evaluate this hypothesis. Single unit extracellular recordings from neurons histologically verified to be in Sm were obtained in urethane/chloralose-anesthetized rats. Noxious but not innocuous mechanical stimulation elicited responses in 75% of the 204 neurons studied. Most (85%) of these neurons were excited, 10% were inhibited and a few neurons (5%) were excited by stimulation at some sites on the body and inhibited from other sites. The receptive fields were usually very large and bilateral. No marked differences were observed in the incidence, response type, or spontaneous activity of neurons located in dorsal, ventral, rostral or caudal parts of Sm. Most of these neurons (99 of 108, 92%) also responded to noxious heating and had a mean threshold of 47 degrees C. The majority of the neurons (19 of 21, 90%) also responded to subcutaneous, intramuscular or intraperitoneal injections of noxious chemicals (formalin or hypertonic saline). The responses elicited by pinching skin or squeezing muscle were frequently facilitated by the subcutaneous or intramuscular injections of formalin. Single electrical stimuli delivered to the cutaneous receptive field rarely produced responses. However, short trains (15-25 msec trains of 200 Hz, 3 msec pulses at 5-10 mA) delivered repetitively elicited responses in 90% (n = 73) of the neurons. These responses appearing after repetitive stimulation frequently resembled the 'wind-up' pattern observed in spinal cord dorsal horn. The conduction velocities of the primary afferents which elicited the Sm neuronal responses as estimated from the latency differences of responses elicited by stimulation at two points along the tail, were indicative of recruitment of A delta and C fibers. These findings provide further support for the proposed role of Sm in thalamic nociceptive mechanisms.

Animals↗
PubMed1992

The afferent and efferent connections of the nucleus submedius in the rat.

The afferent and efferent connections of the nucleus submedius (Sm) in the medial thalamus of the rat were examined. Injections of wheat-germ agglutinin conjugated horseradish peroxidase (WGA-HRP) into the Sm resulted in dense terminal labeling in the middle layers of the ipsilateral ventrolateral orbital cortex (VLO). Less dense labeling was also observed in the superficial and deep layers of VLO and in the medial part of the lateral orbital cortex (LO) and in the contralateral VLO. Retrogradely labeled neurons were observed primarily in the deep layers of VLO and the dorsal peduncular cortex (DP). Labeled neurons were also observed bilaterally, in the nucleus of the horizontal limb of the diagonal band, the lateral hypothalamus, the thalamic reticular nucleus (Rt), medial parabrachial nucleus (MPB), and the laterodorsal tegmental nucleus (LDT). Many labeled neurons were also observed in the trigeminal brain-stem complex. Injections of Fluoro-Gold (FG) into Sm resulted in a very similar distribution of retrogradely labeled neurons. Injections of WGA-HRP and FG in the orbital cortex confirmed the ipsilateral Sm projection to VLO and suggested that the middle and deep layers of VLO receive a specific ipsilateral projection from the dorsal Sm and that the superficial layers receive a projection primarily from the ventral Sm. Injections of WGA-HRP into the lateral hypothalamus, LDT, and MPB confirmed the retrograde labeling findings; the lateral hypothalamus was found to send a projection to the medial Sm, the LDT region to the ventromedial Sm and the MPB to the medial and dorsal Sm. These findings confirm and extend the results of previous studies in cat and rat indicating that Sm has a major and specific reciprocal connection with VLO. This finding, in conjunction with previous studies showing direct spinal and trigeminal inputs and the existence of nociceptive neurons in Sm and VLO, provides further support for a role of Sm in nociception.

Afferent Pathways↗
PubMed1992

Trigeminal and dorsal column nuclei projections to the anterior pretectal nucleus in the rat.

The projections of the trigeminal (V) sensory nuclei (VSN) and the dorsal column nuclei (DCN) to the anterior pretectal nucleus (APT) of the rat were investigated by the use of anterograde and retrograde transport of wheat-germ agglutinin-conjugated horseradish peroxidase (WGA-HRP). Injections of WGA-HRP into the APT retrogradely labeled neurons in the contralateral VSN and DCN. The labeled neurons in the VSN were most concentrated in the rostral V subnucleus interpolaris (Vi), but were also found in caudal V subnucleus oralis (Vo). No labeled neurons were seen in V subnucleus caudalis. In the DCN, retrogradely labeled neurons were observed in rostral portions of both the cuneate (Cu) and gracile (Gr) nuclei. Injections of WGA-HRP into the rostral Vi or caudal Vo resulted in dense anterograde terminal labeling in the ventral two-thirds of the APT; the labeling was maximal in the ventromedial part of the caudal half of the APT and did not extend into its most rostral portion. Labeling resulting from injections of tracer into Cu or Gr was located primarily in the ventral half of the APT, was maximal in the mid-levels of the nucleus and extended into its rostral portions. These results indicate the existence of prominent somatosensory projections to the APT and are consistent with recent findings suggesting a role for the APT in sensorimotor integration.

Animals↗
PubMed1992

Anterior pretectal nucleus-induced modulatory effects on trigeminal brainstem somatosensory neurons.

This study examined the effects of anterior pretectal nucleus (APT) conditioning stimulation on the activity of 92 functionally identified somatosensory brainstem neurons in the trigeminal (V) subnuclei oralis, interpolaris and caudalis of anesthetized rats. Conditioning stimulation inhibited most of the nociceptive neurons and some of the non-nociceptive neurons; facilitation was observed only in some non-nociceptive neurons. These data indicate that the ATP has modulatory effects on both nociceptive and non-nociceptive V somatosensory neurons.

Animals↗
PubMed1991

Trigeminal projections to the nucleus submedius of the thalamus in the rat.

Methods involving the anterograde and retrograde transport of wheat-germ agglutinin conjugated horseradish peroxidase and the retrograde transport of Fluoro-Gold were used in rats to examine the distribution within the spinal trigeminal nucleus of trigeminal neurons projecting to the nucleus submedius (Sm) of the thalamus, as well as the distribution of axon terminals within the Sm. Following injections into the trigeminal nucleus, axon terminals were seen in the dorsal part of the anterior Sm; the terminals occurred bilaterally but had an obvious contralateral dominance. To help determine the precise location of the Sm-petal neurons, the border between trigeminal subnuclei interpolaris and caudalis was examined by the use of immunohistochemical procedures for calcitonin gene-related peptide (CGRP). The Sm-petal neurons that were labeled retrogradely occurred only at the caudal interpolaris and rostral caudalis levels; the number of labeled neurons on the contralateral side was approximately six times that on the ipsilateral side. Most of these neurons were located in the ventral part of the caudal interpolaris and rostral caudalis and spinal trigeminal tract; in caudalis, the neurons were almost exclusively localized to its superficial layers. There were approximately three times more labeled neurons in interpolaris than in caudalis. In the experiments combined with immunohistochemistry for CGRP, many neurons (34%) were seen in proximity to CGRP-like immunopositive fibers. These results suggest that the Sm of the rat receives its orofacial afferent inputs from brainstem neurons that are localized to the caudal interpolaris and rostral caudalis. In view of previous studies that have implicated these three structures in somatosensory function, and in particular nociception, our data point to a role for this direct projection from interpolaris and caudalis to Sm in the central processing of pain.

Animals↗
PubMed1991

Periaqueductal gray matter and nucleus raphe magnus involvement in anterior pretectal nucleus-induced inhibition of jaw-opening reflex in rats.

In previous studies we have shown that electrical stimulation of the cortex or anterior pretectal nucleus (APT) inhibits the jaw-opening reflex (JOR). In the present study we investigated whether these effects are mediated by a relay in the periaqueductal gray matter (PAG) or rostroventromedial medulla (RVM). Experiments were performed on chloralose-urethane anesthetized rats. The JOR which was elicited by electrical stimulation of the mandibular incisor tooth was monitored by recording the evoked digastric muscle activity. Conditioning stimulation (20 ms train of 0.2 ms pulses at 400 Hz) was delivered to the facial area of the sensorimotor cortex, APT, PAG or nucleus raphe magnus (NRM) 50 ms prior to the test stimulus to the tooth that evoked the JOR. In addition, the effects of microinjections of glutamate into APT, PAG and NRM on the tooth-evoked JOR were also evaluated. The inhibition of the JOR by electrical and glutamate conditioning stimulation was found to be most potent for activation of the NRM and least potent for the APT. Local anesthetic (2% lidocaine, 0.3-0.6 microliters) block of the PAG could partially, significantly (P less than 0.05) and reversibly reduce both the APT and cortical-induced depression of the JOR. Lidocaine block of the ventromedial pons reversibly reduced the PAG, APT and cortical-induced inhibition of the JOR (P less than 0.05). Lidocaine block of the lateral RVM had powerfully (P less than 0.01) and reversibly reduced the PAG-induced inhibition, but had only a small effect (P less than 0.05) on the APT-induced inhibition and no significant effect on the cortical-induced inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Role of anterior pretectal nucleus in somatosensory cortical descending modulation of jaw-opening reflex in rats.

Both the somatosensory cerebral cortex and anterior pretectal nucleus (APT) have been shown to produce descending modulation of trigeminal (V) and spinal somatosensory neurone and reflex activities. Since the APT receives a direct projection from the somatosensory cortex, experiments were performed to compare the effects of APT and somatosensory cortex stimulation on the jaw-opening reflex (JOR) and to examine the possible involvement of APT in corticofugal modulation. Conditioning stimulation of the ipsilateral or contralateral somatosensory cortex in chloralose-urethane anaesthetized rats induced inhibition of the JOR elicited by test stimulation of the maxillary skin or tooth pulp, at conditioning-test intervals between 30 and 200 ms. A similar time course of inhibition of the JOR was noted with APT conditioning stimulation. Local unilateral injection of 2% lidocaine (0.3-0.6 microliter) into APT could partially and reversibly reduce the ipsilateral cortically evoked inhibition of the JOR. Ibotenic acid (5 micrograms, 0.5 microliter)-induced unilateral lesions of APT and its adjoining structures also greatly reduced the ipsilateral cortically induced inhibition of the JOR. Histological reconstruction of APT lesion sites and data analysis indicated that this reduction in the corticofugal inhibition was proportionally and significantly related to the extent of damage to APT, but not to its adjoining structures. These findings collectively suggest that the cortically-induced inhibition of the JOR is at least partly mediated by a relay in the APT.

Animals↗
PubMed1990

Physicochemical properties of carbovir, a potential anti-HIV agent.

(+-)-Carbovir [(+-)-9-[4 alpha-(hydroxymethyl)-cyclopent-2-ene-1 alpha-yl]guanine; NSC 614846] is a novel carbocyclic nucleoside analogue which has been shown to be a potent and selective inhibitor of HIV in vitro. As part of an effort to develop a parenteral formulation for subsequent clinical and toxicological evaluation of this compound, the aqueous solution stability of carbovir as a function of pH and temperature and various physicochemical properties of carbovir including its pKa, solubility versus pH and solvent composition, and octanol-water partition coefficient have been examined. Ultraviolet spectrophotometry indicated that carbovir has pKa values of 3.15 and 9.68, respectively, at 25 degrees C and 0.01 ionic strength. The aqueous solubility of carbovir over the pH range 7-10.5 was consistent with that expected of a weak acid with a pKa of 9.65 and an intrinsic solubility of 1.24 mg/mL. Due to the limited solubility of carbovir at physiological pH, methods for solubilizing carbovir in aqueous solution were explored, including propylene glycol-water cosolvents and complexation with hydroxypropyl-beta-cyclodextrin. As expected for carbovir, a semipolar compound with an octanol-water partition coefficient of 0.29, propylene glycol:water cosolvents were not highly effective in enhancing solubility. Complex formation between carbovir and 2-hydroxypropyl-beta-cyclodextrin was found to be more effective, with a K1:1 of 105 M-1 for the complexation. The pH profiles generated at 50, 70, and 90 degrees C were accounted for by acid-catalyzed degradation at low pH leading to the formation of guanine and a neutral degradation pathway which dominates above pH 4. Prototype lyophilized formulations containing (after reconstitution) 10 mg/mL of carbovir at a pH of 10.6 were developed and evaluated.

2-Hydroxypropyl-beta-cyclodextrin↗